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(45) Date of grant: 04/09/2008
 
(19) Kenya Industrial Property Institute.
(12) PATENT
(51) Int.C1.7: 0 1N 43/90, C 07D 471/04
(21)Application    KE/P/ 2003/ 000315    (84) WO No. 2004/056825 Al
Number:    08/07/2004
(22)Filing Date:    03/12/2003
(31)Priority Number: 230020 23/12/2002 GB    (32) Date: (33) Country:
(73)    Owner(s): SYNGENTA PARTICIPATIONS AG of SCHWARZWALDALLEE 215 CH-4058 BASEL, U.S.A. and SYNGENTA LTD of Pristeley Road Surrey Research, United Kingdom
(72) Inventor(s)    CROWLEY, PATRICK JELF; DOBLER, MARKUS;
MULLER, URS and WILLIAMS, JOHN
(74)    Agent/address for correspondence: Hamilton Harrison & Mathews, P.O. Box 30333-00100, Nairobi
(54) Title:    PYRIDODIAZINES AS PLANT FUNGICIDES
(57) Abstract: Fungicidal compounds of the general formula wherein R,R1,R2,W,X,Y and Z are as defined inthe specification
 
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PYRIDODIAZINES AS PLANT FUNGICIDES
This invention relates to novel derivatives of pyridopyrazines and pyridopyridazines, to processes for preparing them, to certain intermediate chemicals used in their manufacture, to compositions containing them and to methods of using them to combat fungi, especially
5    fungal infections of plants.
Derivatives of the nitrogen-containing 5,6 ring system s-1,2,4-triazolo[1,5-a]pyri¬midine are known from the patent literature as being useful for controlling phytopathogenic
fungi. Examples of recent patent publications include EP-A-1249452, WO 02/051845, WO 02/083676, WO 02/083677, WO 02/088125, WO 02/088126, WO 02/088127.
10 Condensed nitrogen heterocycles used as antimycotics are known from US 5821244.
Derivatives of pyridopyrazines are known in the chemical literature, for example from J. Med. Chem. (1968), 11(6), 1216-18, J. Med. Chem. (1970), 13(5), 853-7 and US 3984412, but not for agrochemical purposes.
The present invention is concerned with the provision of novel pyridopyrazines and 15 pyridopyridazines for combating phytopathogenic diseases on plants and harvested food crops.
Thus, according to the present invention, there is provided a compound of the general formula (1):
 

 
20- wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(C14)alkyl;
R is halo;
R' is halo, C1.8 alkyl, C2_8 alkenyl, C2_8 alkynyl, C3_8cycloalkyl, C3_8 cycIoalkyl(C1_6)alkyl,
25    C1_8 alkoxy,    alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio,
aryl(C1.4)alkyl, aryl(Ci4alkoxy, heteroaryl(Ci4alkyl, heteroaryl(Ci4)alkoxy, aryl(C14)alkylthio, heteroaryl(Ci4)alkylthio, morpholino, piperidino or pyrrolidino;
R2 is NR3R4;
R3 and R4 are independently H, CI-8 alkyl, C2.8 alkenyl, C2-8 alkynyl, aryl, aryl(Ci_g)alkyl,
30    C3.8 cycloalkyl, C3_8 cycloalkyl(C1_6)alkyl, heteroaryl, heteroaryl(C1_8)alkyl, NR5R6, provided
 
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that not both R3 and R4 are H or NR5R6, or
R3 and R4 together form a C3_7 alkylene or C3_7 alkenylene chain optionally substituted with one or more C14 alkyl or C14 alkoxy groups, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine,
    5    thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazine N-(C1.4)alkyl (especially N-methyl) ring; and
R5 and R6 are independently H, C1_8 alkyl, C2_8 alkenyl, C2_8 alkynyl, aryl, aryl(C1_8)alkyl, C3_8 cycloalkyl, C3-8 cycloalkyl(C1_6)alkyl, heteroaryl or heteroaryl(C1_8)alkyl;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
    10    R8) being optionally substituted with halogen, cyano, C1_6 alkoxy, C1_6 alkylcarbonyl,
C14alkoxycarbonyl, C1_6 haloalkoxy, C1_6 alkylthio, tri(C1.4)alkylsilyl, C1_6 alkylamino or CI _6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C14 alkyl (especially methyl), and
    15    any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with
one or more substituents selected from halo, hydroxy, mercapto, C1_6 alkyl, C2_6 alkenyl,
C2_6 alkynyl, C1_6 alkoxy, C2-6 alkenyloxy, C2,6 alkynyloxy, halo(C1_6)alkyl, halo(C1_6)alkoxy, C1.6 alkylthio, halo(C1.6)alkylthio, hydroxy(C1_6)alkyl, C14 alkoxy(C1_6)alkyl, C3_6 cycloalkyl, C3_6 cycloalkyl(C14alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato,
20 isothiocyanato, nitro, -NR"'R"", -NHCORm, -NHCONR"'R"", -CONR"'R'"', -SO2R"',
-0S02R-, -COR'", -CR-=NR"" or -N=CR-R"", in which R"' and R"" are independently hydrogen, C14 alkyl, halo(C14alkyl, C14 alkoxy, halo(C14)alkoxy, C14 alkylthio,
C3_6 cycloalkyl, C3_6 cycloalkyl(C14alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally-substituted with halogen, C14 alkyl or C14 alkoxy.
    25    The invention includes a compound of the general formula (1) as defined
immediately above except that: C1_8 alkoxy and C1_8 alkylthio are excluded as values of R and R2; C7 alkylene and C3_7 alkenylene are excluded as chains formed by R3 and R4; the C3_6 chain that R3 and R4 may form may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and
 30 piperazine are excluded as rings that R3 and R4 may form; tri(C14)alkylsily1 is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety and any morpholine, piperidine or pyrrolidine ring is unsubstituted.
 
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The compounds of the invention may contain one or more asymmetric carbon atoms and may exist as enantiomers (or as pairs of diastereoisomers) or as mixtures of such. They may also exist as diastereoisomers by virtue of restricted rotation about a bond. However, mixtures of enantiomers or diastereoisomers may be separated into individual isomers or
5    isomer pairs, and this invention embraces such isomers and mixtures thereof in all
proportions. It is to be expected that for any given compound, one isomer may be more fungicidally active than another.
Except where otherwise stated, alkyl groups and alkyl moieties of alkoxy, alkylthio, etc., contain from 1 to 8, suitably from 1 to 6 and typically from 1 to 4, carbon atoms in the
10    form of straight or branched chains. Examples are methyl, ethyl, n- and iso-propyl, n-, sec-,
iso- and tert-butyl, n-pentyl and n-hexyl. Cycloalkyl groups contain from 3 to 8, typically from 3 to 6, carbon atoms and include bicycloalkyl groups such as the bicyclo[2.2.1]heptyl
group. Haloalkyl groups or moieties are typically trichloromethyl or trifluoromethyl or contain a trichloromethyl or trifluoromethyl terminal group.
15    Except where otherwise stated, alkenyl and alkynyl moieties also contain from 2 to 8,
suitably from 2 to 6 and typically from 2 to 4, carbon atoms in the form of straight or
branched chains. Examples are allyl, 2-methylallyl and propargyl. Optional substituents include halo, typically fluoro. An example of halo-substituted alkenyl is 3,4,4-trifluoro-n-butenyl.
20    Halo includes fluoro, chloro, bromo and iodo. Most commonly it is fluoro, chloro or
bromo and usually fluoro or chloro.
Aryl is usually phenyl but also includes naphthyl, anthryl and phenanthryl.
Heteroaryl is typically a 5- or 6-membered aromatic ring containing one or more 0, N or S heteroatoms, which may be fused to one or more other aromatic or heteroaromatic
25        rings, such as a benzene ring. Examples are thienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl,
oxadiazolyl, pyrazolyl, imidazolyl, triazolyl, isothiazolyl, tetrazolyl, thiadiazolyl, pyridyl,
pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, benzofuryl, benzothienyl, dibenzofuryl, benzothiazolyl, benzoxazolyl, benzimidazolyl, indolyl, quinolinyl and quinoxalinyl groups and, where appropriate, N-oxides thereof.
30    The 6,6-ring systems embraced by the general formula (1) are pyrido[2,3-c]pyri-
dazines (where W and X are both CR8 and Y and Z are both N), pyrido[2,3-d]pyridazines (where W and Z are both CR8 and X and Y are both N), pyrido[3,2-c]pyridazines (where Y
-4-
and Z are both CR8 and W and X are both N) and pyridof2,3-b]pyrazine (where X and Y are both CR8 and W and Z are both N). Of particular interest are pyrido[2,3-b]pyrazines.
R8, which may be the same or different for the two CR8 values of W, X, Y and Z, is
14, halo (for example bromo), C14 alkyl (for example methyl), C1-4 alkoxy (for example
5    methoxy) or halo(Ci4alkyl (for example trifluoromethyl). Usually R8 will be H.
R is halo, especially chloro or fluoro, and R2 is NR3R4 . In the case of pyrido[2,3-blpyrazine ring systems, the more active compounds are those where R2 is NR3R4. R3 is typically C1-8 alkyl (for example ethyl, n-propyl, n-butyl, sec-butyl (the S- or R-isomer or the racemate) and tert-butyl), halo(C1.8)alkyl (for example 2,2,2-trifluoroethyl,
10    2,2,2-trifluoro-l-methylethyl (the S- or R-isomer or the racemate), 3,3,3-trifluoropropyl and
4,4,4-trifluorobutyl), hydroxy(C1_8)alkyl (for example hydroxyethyl), C14 alkoxy(C14)alkyl (for example methoxymethyl and methoxy-iso-butyl), C14 alkoxyhalo(C1_8)alkyl (for example 2-methoxy-2-trifluromethylethyl), tri(C1.4)alkylsilyl(Ci_6)alkyl(for example trimethylsilylmethyl), C14 alkylcarbonyl(Ci_8)alkyl (for example 1-acetylethyl and 1-tert-
15    butylcarbonylethyl), C14 alkylcarbonylhalo(C1_8)alkyl (for example 1-acety1-2,2,2-
trifluoroethyl), phenyl(14)alkyl (for example benzyl), C2.8 alkenyl (for example allyl and methylallyl), halo(C2_8)alkenyl (for example 3-methyl-4,4-difluorobut-3-enyl), C2_8 alkynyl (for example propargyl), C3_8 cycloalkyl (for example cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl) optionally substituted with chloro, fluoro or methyl, C3-8 cycloal-
20 kyl(Ci_4)alkyl (for example cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl), phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo (typically fluoro, chloro or bromo), C1_4 alkyl (typically methyl), halo(Ci_4)alkyl (typically trifluoromethyl), C14 alkoxy (typically methoxy) and halo(C1.4)alkoxy (typically
25    trifluoromethoxy). R4 is typically H, C14 alkyl (for example ethyl and n-propyl),
halo(Ci4alkyl (for example 2,2,2-trifluoroethyl) or amino. Alternatively R3 and R4 together form a C4_6 alkylene chain optionally substituted with methyl, for example 3-methylpentylene, or, together with the nitrogen atom to which they are attached, R3 and R4 .form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide
30        ring or a piperazine or piperazine N-(Ci_4)alkyl (especially N-methyl) ring, in which the
morpholine or piperazine rings are optionally substituted with methyl.
Typically R' is phenyl optionally substituted with from one to five halogen atoms, particularly fluorine and chlorine atoms and especially fluorine atoms or with from one to
 
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three substituents selected from halo (for example fluoro and chloro), C14 alkyl (for example methyl), halo(C1..4)alkyl (for example trifluoromethyl), C14 alkoxy (for example methoxy) or halo(C14)alkoxy (for example trifluoromethoxy). Examples are 2,6-difluorophenyl, 2-fluoro¬6-chiorophenyl, 2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl, 2,6-difluoro-4-methoxyphenyl,
    5    pentafluorophenyl, 2-fluorophenyl, 2,3,5,6-tetrafluorophenyl, 2-chloro-4,6-difluorophenyl,
2-chlorophenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl, 2,4,6-trichlorophenyl, 2,3,6-tri-chlorophenyl, pentachlorophenyl, 2-fluoro-4,6-dichlorophenyl, 4-fluoro-2,6-dichlorophenyl, 2-bromophenyl, 2-fluoro-6-bromophenyl, 2-bromo-4,6-difluorophenyl, 2-fluoro-6-methyl-
phenyl, 2-chloro-6-methylphenyl, 2-methoxyphenyl, 2,6-dimethoxyphenyl, 2-fluoro-6-
    10    methoxyphenyl, 2-trifluoromethylphenyl, 2-fluoro-6-trifluoromethylphenyl, 2,6-di-(trifluoro-
methyl)phenyl, 2-chloro-6-trifluoromethylphenyl, 2,4-difluoro-6-trifluoromethylphenyl, 2,4-difluoro-6-methoxyphenyl and 2,4-difluoro-6-methylphenyl.
Also of particular interest are compounds where R1 is pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from
    15    halo (for example fluoro and chloro), C14 alkyl (for example methyl), halo(C14)alkyl (for
example trifluoromethyl), C14 alkoxy (for example methoxy) or halo(C14)alkoxy (for
example trifluoromethoxy). Examples are 2,4-difluoropyrid-3-yl, 3,5-difluoropyrid-4-yl, tetrafluoropyrid-4-yl, 3-fluoropyrid-2-yl, 4-fluoropyrid-3-yl, 3-fluoropyrid-4-yl, 2-fluoro-pyrid-3-yl, 2,4,6-trifluoropyrid-3-yl, 3,5-difluoropyrid-2-yl, 2,6-difluoropyrid-3-yl,
 20 2,4-difluoro-6-methoxypyrid-3-yl, 2-fluoro-4-chloropyrid-3-yl, 3-fluoro-5-chloropyrid-4-yl, 2-chloro-4-fluoropyrid-3-yl, 2,4-dichloropyrid-3-yl, 3-chloropyrid-2-yl I, 4-chloropyrid-3-yl, 3-chloropyrid-4-yl, 2-chloropyrid-3-yl, 3-trifluoromethylpyrid-2-yl, 4-trifluoromethylpyrid¬3-yl, 3,5-dichloropyrid-2-yl, 4,6-dichloropyrid-3-yl, 3-trifluoromethylpyrid-4-yl, 2-trifluoro¬methylpyrid-3-yl, 2-fluoro-4-trifluoromethylpyrid-3-yl, 3-fluoro-5-trifluoromethylpyrid-4-yl,
    25    4-fluoro-2-trifluoromethylpyrid-3-yl, 2,6-dichloropyrid-3-yl, 3,5-dichloropyrid-4-yl,
3-chloro-6-trifluoromethylpyrid-2-yl, 3-fluoro-6-trifluoromethylpyrid-2-yl, pyrid-2-yl, pyrid¬3-yl and pyrid-4-yl.
Also of particular interest are compounds where RI is 2- or 3-thienyl optionally
substituted with from one to three halogen atoms or with from one to three substituents
    30    selected from halo (for example fluoro and chloro), C14 alkyl (for example methyl), halo-
(C1 )alkyl (for example trifluoromethyl), CIA alkoxy (for example methoxy) or halo(C14alkoxy (for example trifluoromethoxy). Examples are 3-fluorothien-2-yl,
 
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3-chlorothien-2-yl, 2,4-difluorothien-3-yl, 2,4-dichlorothien-3-yl and 2,4,5-tri-chlorothien-3-yl.
Examples of other values of RI of especial interest are unsubstituted piperidino and
morpholino, 2-methylpiperidino, 2,6-dimethylpiperidino and 2,6-dimethylmorpholino.
5        In one aspect the invention provides a compound of the general formula (1) wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(C14)alkyl;
R is halo;
R1 is halo, C1_8 alkyl, C2_8 alkenyl, C2.8 alkynyl, C3_8 cycloalkyl, C3_8 cycloalkyl(Ci_6)alkyl,
10    C1,8 alkoxy, C1_8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio,
aryl(Ci_4)alkyl, aryl(Ci4)alkoxy, heteroaryl(C14)alkyl, heteroaryl(C1_4)alkoxy, aryl(C1_4)alkylthio, heteroaryl(Ci4alkylthio, morpholino, piperidino or pyrrolidino;
R2 is NR3R4;
R3 and R4 are independently H, Cls alkyl, C2.8 alkenyl, C2-8 alkynyl, aryl, aryl(C1_8)alkyl,
15        C3_8 cycloalkyl, C3_8 cycloalkyl(C1.6)alkyl, heteroaryl, heteroaryl(C1_8)alkyl, NR5R6, provided
that not both R3 and R4 are H or NR5R6, or
R3 and R4 together form a C3_7 alkylene or C3_7 alkenylene chain optionally substituted with one or more C14 alkyl or C14 alkoxy groups, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine,
20        thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazine N-(C1-4)alkyl (especially N-methyl) ring; and
R5 and R6 are independently H, C1_8 alkyl, C2.8 alkenyl, C2.8 alkynyl, aryl, aryl(C1_8)alkyl, C3_8 cycloalkyl, C3-8 cycloalkyl(C1_6)alkyl, heteroaryl or heteroaryl(C1_8)alkyl;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
25    R8) being optionally substituted with halogen, cyano, C1_6 alkoxy, C1.6 alkylcarbonyl,
C1_6alkoxycarbonyl, C1_6 haloalkoxy, C1_6 alkylthio, tri(C1_4)alkylsilyl, C1.6 alkylamino or C1_6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C14 alkyl (especially methyl), and
30    any of the foregoing aryl, heteroaryl, aryloxy or heteroaryl groups being optionally
substituted with one or more substituents selected from halo, hydroxy, mercapto, C1_6 alkyl, C2.6 alkenyl, C2_6 alkynyl, C1_6 alkoxy, C2_6 alkenyloxy, C2_6 alkynyloxy, halo(Ci_6)alkyl, halo(C1,6)alkoxy, C1,6 alkylthio, halo(C1_6)alkylthio, hydroxy(C1.6)alkyl,
 
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C14 alkoxy(C1_6)alkyl, C3_6 cycloalkyl, C3_6 cycloalkyl(Ci4alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, -NR-R"", -NHCOR"', - NHCONR-R-, -CONR'"R"", -S021r, -0S02R-, -COR"', -CR"'=NR"" or -N=CR-R-, in which R"' and R"" are independently hydrogen, CIA alkyl, halo(C1.4)alkyl, C1.4 alkoxy, halo-
    5    (C1_4)alkoxy, C14 alkylthio, C3_6 cycloalkyl, C3_6 cycloalkyl(C14alkyl, phenyl or benzyl, the
phenyl and benzyl groups being optionally substituted with halogen, C14 alkyl or
C1_4 alkoxy.
Of particular interest are compounds where W and Z are both N and X and Y are both CH.
The invention includes a compound of the general formula (1) as defined
    10    immediately above except that: C7 alkylene and C3_7 alkenylene are excluded as chains
formed by R3 and R4; the C3.4 chain that R3 and R4 may form may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R3 and R4 may form; tri(C14)alkylsily1 is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl
    15    group or moiety, and any morpholine, piperidine or pyrrolidine ring is unsubstituted.
In another aspect the invention provides a compound of the general formula (1) wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CRg;
R8 is H, halo, C14 alkyl, CI-4 alkoxy or halo(C14alkyl;
    20    R is halo;
R' is halo, C1.8 alkyl, C2_8 alkenyl,    alkynyl, Cmcycloalkyl, C3.8 cycloalkyl(C1..6)alkyl,
Ci_g alkoxy, C1_8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C14)alkyl, aryl(Ci4)alkoxy, heteroaryl(C14)alkyl, heteroaryl(C14alkoxy, aryl(C14)alkylthio, heteroaryl(C14)alkylthio, morpholino, piperidino or pyrrolidino;
25 R2 is NR3R4;
R3 is C14 alkyl, halo(CIA)alkyl, C2.4 alkenyl, C3_6 cycloalkyl, C3_6 cycloalkyl(CIA)alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three subs¬tituents selected from halo, C14 alkyl, halo(CIA)alkyl, C14 alkoxy and halo(C14)alkoxy; and
R4 is H, C1.4 alkyl or amino, or
    30    R3 and R4 together form a C4_6 alkylene chain optionally substituted with C14 alkyl or
C14 alkoxy, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
 
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piperazine N-(Ci_4)alkyl (especially N-methyl) ring;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R8) being optionally substituted with halogen, cyano, C1.6 alkoxy, C1_6 alkylcarbonyl,
C1_6 alkoxycarbonyl, C1_6 haloalkoxy, C1_6 alkylthio, tri(C14alkylsilyl, C1_6 alkylamino or
    5    C1_6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C14 alkyl (especially methyl), and
any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with
one or more substituents selected from halo, hydroxy, mercapto, C1-6 alkyl, C2_6 alkenyl,
    10    C2_6 alkynyl, C1_6 alkoxy, C2-6 alkenyloxy, C2_6 alkynyloxy, halo(C1_6)alkyl, halo(C1-6)alkoxy,
C1.6 alkylthio, halo(C1_6)alkylthio, hydroxy(C1_6)alkyl, C1.4 alkoxy(C1_6)alkyl, C3.6 cycloalkyl, C3_6 cycloalkyl(Ci4alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, -NR"'R"", -NHCOR'", -NHCONR"'R'"', -CONR'"R'"', -S021r,
-0S02R"', -COR"', -CR"I=NR"" or -N=CR-R"", in which R"' and R"" are independently
    15    hydrogen, C14 alkyl, halo(Ci_4)alkyl, C14 alkoxy, halo(C1.4)alkoxy, Ci4 alkylthio,
C3_6 cycloalkyl, C3_6 cycloalkyl(C14alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C14 alkyl or C14 alkoxy.
Of particular interest are compounds where W and Z are both N and X and Y are both CH.
The invention includes a compound of the general formula (1) as defined
20 immediately above except that: the C4_6 chain that R3 and R4 may form may only be optionally substituted with methyl; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R3 and R4 may form; tri(C14)alkylsily1 is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and any morpholine, piperidine or pyrrolidine ring is unsubstituted.
    25    In yet another aspect the invention provides a compound of the general formula (1)
wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(C14)alkyl;
R is halo;
    30    R' is optionally substituted phenyl;
R2 is NR3R4;
R3 and R4 are independently H, C1_8 alkyl, C2_8 alkenyl, C2_8 alkynyl, aryl, aryl(C1_8)alkyl, cycloalkyl, C3_8 cycloalkyl(C1_6)alkyl, heteroaryl, heteroaryl(C1_8)alkyl, NR5R6, provided
 
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that not both R3 and R4 are H or NR5R6, or
R3 and R4 together form a C3_7 alkylene or C3_7 alkenylene chain optionally substituted with one or more C14 alkyl or C14 alkoxy groups, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine,
    5    thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazine N-(C14)alkyl (especially N-methyl) ring; and
R5 and R6 are independently H, C1_8 alkyl, C2-8 alkenyl, C2_g alkynyl, aryl, aryl(C1_8)alkyl, C3_8cycloalkyl, C3_8cycloalkyl(C1_6)alkyl, heteroaryl or heteroaryl(C1_8)alkyl;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
    10    R8) being optionally substituted with halogen, cyano, C1_6 alkoxy, C1_6 alkylcarbonyl,
C1.6 alkoxycarbonyl, C1-6 haloalkoxy, C1_6 alkylthio, tri(C14alkylsilyl, C1_6 alkylamino or C1_6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C14 alkyl (especially methyl), and
    15    any of the foregoing aryl or heteroaryl groups or moieties, including the phenyl group of R',
being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C1_6 alkyl, C2-6 alkenyl, C2_6 alkynyl, C1_6 allcoxy, C2_6 alkenyloxy,
C2_6 alkynyloxy, halo(C1.6)alkyl, halo(C14alkoxy, C1_6 alkylthio, halo(C14)alkylthio, hydroxy(C1_6)alkyl, C14 alkoxy(C1_6)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(Ci4alkyl,
    20    phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro,
-NR-12."", -NHCOR'", -NHCONR"'R'"', -CONR"'R"", -S021r, -0S02R"', -COW", -CR—=NR"" or -N=CR"'R"", in which R"' and R"" are independently hydrogen, C14 alkyl, halo(C1_4)alkyl, C14 alkoxy, halo(Cm)alkoxy, C1-4 alkylthio, C3-6 cycloalkyl,
C3_6 cycloalkyl(C14)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally
    25    substituted with halogen, Cm alkyl or C14 alkoxy. Of particular interest are compounds
where W and Z are both N and X and Y are both CH.
The invention includes a compound of the general formula (l) as defined
immediately above except that: Ci_g alkoxy and Cl_g alkylthio are excluded as values of R
and R2; C7 alkylene and C3_7 alkenylene are excluded as chains formed by R3 and R4; the C1.6
30 chain that R3 and R4 may form may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R3 and R4 may form; tri(C14)alkylsily1 is excluded as a substituent
 
- 10-
of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and the morpholine ring that R3 and R4 may form is unsubstituted.
In still yet another aspect the invention provides a compound of the general formula
(I) wherein W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
    5    R8 is H, halo(e.g. fluoro, chloro or bromo), C14 alkyl (e.g. methyl), Ci4 alkoxy (e.g.
methoxy) or halo(C14)alkyl (e.g. trifluoromethyl);
R is halo (e.g. fluoro, chloro or bromo);
R' is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C14 alkyl, halo(Ci.4)alkyl, C1_4 alkoxy or
    10    halo(C1_4) alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with
from one to three substituents selected from halo, C14 alkyl, halo(C1.4)alkyl, C14 alkoxy or halo(Ci_4)alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C14 alkyl, halo(Ci_4)alkyl,
C/4 alkoxy or halo(Ci_4)alkoxy, or piperidino or morpholino both optionally substituted with
15 one or two methyl groups;
R2 is NR3R4;
R3 is C1_8 alkyl, halo(C1_8)alkyl, hydroxy(C1_8)alkyl, C14 alkoxy(Ci_8)alkyl, C1_4 alkoxyhalo-(C1_8)alkyl, tri(C14alkylsily1(Ci_6)alkyl, C1-4 alkylcarbonyl(C1_8)alkyl, C14 alkylcarbonyl-halo(C1.8)alkyl, pheny1(1_4)alkyl, C2_8 alkenyl, halo(C2_8)alkenyl, C2.8 alkynyl, C3_8 cycloalkyl
    20    optionally substituted with chloro, fluoro or methyl, C3-8 cycloalkyl(Ci4alkyl, phenylamino,
piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C14 alkyl, halo(Ci4alkyl, C14 alkoxy and halo(Q.4)alkoxy; and
R4 is H, C14 alkyl, halo(C1_4)alkyl or amino, or
    25    R3 and R4 together form a C3_7 alkylene or C3_7 alkenylene chain optionally substituted with
methyl, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N-(C1_4)alkyl (especially N-methyl) ring, in which the morpholine or piperazine
    30    rings are optionally substituted with methyl.
Of particular interest are compounds where W and Z are both N and X and Y are both CH. In still yet another aspect the invention provides a compound of the general formula (1) wherein
 
-    11 -
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(C14)alkyl;
R is halo;
RI is phenyl optionally substituted with from one to five halogen atoms or with from one to 5    three substituents selected from halo, C14 alkyl, halo(C14)alkyl, C1_4 alkoxy or
halo(C14) alkoxy;
R2 is NR3R4;
R3 is C14 alkyl, halO(C1-4)alkyl, C24 alkenyl, C3-6 cycloalkyl, C3-6 CyClOalkyl(C14)alkyl or
phenylamino in which the phenyl ring is optionally substituted with one, two or three
10        substituents selected from halo, C14 alkyl, halo(C14alkyl, C14 alkoxy and halo(C14)alkoxy;
and
R4 is H, C14 alkyl or amino, or R3 and R4 together form a C4-6 alkylene chain optionally substituted with methyl, or, together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine ring.
15 Of particular interest are compounds where W and Z are both N and X and Y are both CH. Compounds that form part of the invention are illustrated in Tables 1 to 127 below. Characterising data are given later in the Examples and in Table 133.
In Table 1 the compounds have the general formula (1 A), where W and Z are N, X and Y are CH, R is Cl, R' is 2,4,6-trifluorophenyl and R3 and R4 are as shown in the table. R4N,R3
20
Table 1          (1A)
               
 
- 12 -
 
- 13-
 
- 14
 
- 15 -
 
- 16-
 
- 17 -
 
-18-
 
- 19-
 
- 20 -
 
- 21 -
 

 
Table 2
Table 2 consists of 662 compounds of the general formula (I A), where W and Z are
    5    N, X and Y are CH, R is CI, R' is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 2 is the same as compound 1 of Table 1 except that in compound 1 of Table 2, R' is 2,5,6-trifluorophenyl. Similarly, compounds 2 to 662 of
Table 2 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 2, R' is 2,5,6-trifluorophenyl.
10 Table 3
Table 3 consists of 662 compounds of the general formula (1 A), where W and Z are
N, X and Y are CH, R is CI, RI is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 3 is the same as compound 1 of Table 1 except that in compound 1 of Table 3, R' is 2,3,4,5,6-pentafluorophenyl. Similarly,
15 compounds 2 to 662 of Table 3 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 3, R' is 2,3,4,5,6-pentafluorophenyl.
Table 4
Table 4 consists of 662 compounds of the general formula (1 A), where W and Z are
N, X and Y are CH, R is Cl, R' is 2,6-difluoro-4-methoxyphenyl, and the values of R3 and R4
    20    are as listed in Table 1. Thus, compound I of Table 4 is the same as compound I of Table 1
except that in compound 1 of Table 4, R' is 2,6-difluoro-4-methoxyphenyl. Similarly, compounds 2 to 662 of Table 4 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 4, R' is 2,6-difluoro-4-methoxyphenyl.
Table 5
    25    Table 5 consists of 662 compounds of the general formula ( 1 A), where W and Z are
N, X and Y are CH, R is Cl, R' is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are
as listed in Table 1. Thus, compound 1 of Table 5 is the same as compound 1 of Table I except that in compound I of Table 5, R' is 2-fluoro-6-chlorophenyl. Similarly, compounds
 
-22-
2 to 662 of Table 5 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 5, R' is 2-fluoro-6-chlorophenyl.
Table 11
Table 11 consists of 662 compounds of the general formula (1 A), where W and X are
    5    N and Y and Z are CH, R is Cl, R' is 2,4,6-trifluorophenyl, and the values of R3 and R4 are
as listed in Table I. Thus, compound 1 of Table 11 is the same as compound 1 of Table I
except that in compound I of Table 11, the compound has the general formula (IA) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 11 are the same as compounds 2 to 662 of Table I except that in the compounds of Table 11, the compounds
10 have the general formula (IA) where W and X are N and Y and Z are CH.
Table 12
Table 12 consists of 662 compounds of the general formula (IA), where W and X are N and Y and Z are CH, R is Cl, R' is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 12 is the same as compound 1 of Table 2
15 except that in compound 1 of Table 12, the compound has the general formula (1A) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 12 are the same as compounds 2 to 662 of Table 2 except that in the compounds of Table 12, the compounds have the general formula (1A) where W and X are N and Y and Z are CH.
Table 13
    20    Table 13 consists of 662 compounds of the general formula (1A), where W and X are
N and Y and Z are CH, R is Cl, R' is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and
R4 are as listed in Table 1_ Thus, compound 1 of Table 13 is the same as compound 1 of Table 3 except that in compound 1 of Table 13, the compound has the general formula (IA) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 13 are
25 the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 13, the
compounds have the general formula (1 A) where W and X are N and Y and Z are CH. Table 14
Table 14 consists of 662 compounds of the general formula (1A), where W and X are N and Y and Z are CH, R is CI, R' is 2,6-difluoro-4-methoxyphenyl, and the values of R3
 30 and R4 are as listed in Table 1. Thus, compound 1 of Table 14 is the same as compound 1 of Table 4 except that in compound 1 of Table 14, the compound has the general formula ( IA) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 14 are
 
-23-
the same as compounds 2 to 662 of Table 4 except that in the compounds of Table 14, the
compounds have the general formula (I A) where W and X are N and Y and Z are CH. Table 15
Table 15 consists of 662 compounds of the general formula (IA), where W and X are
 5 N and Y and Z are CH, R is Cl, R' is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound I of Table 15 is the same as compound 1 of Table 5 except that in compound 1 of Table 15, the compound has the general formula (IA) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 15 are the same as compounds 2 to 662 of Table 5 except that in the compounds of Table 15, the compounds
10 have the general formula (1A) where W and X are N and Y and Z are CH.
Table 21
Table 21 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is Cl, R1 is 2,4,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 21 is the same as compound 1 of Table 1
15 except that in compound 1 of Table 21, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 21 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 21, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.
Table 22
    20    Table 22 consists of 662 compounds of the general formula (1A), where W and Z are
CH and X and Y are N, R is Cl, R' is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 22 is the same as compound 1 of Table 2 except that in compound I of Table 22, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 22 are the same as
25 compounds 2 to 662 of Table 2 except that in the compounds of Table 22, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.
Table 23
Table 23 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is CI, R' is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and
    30    R4 are as listed in Table 1. Thus, compound 1 of Table 23 is the same as compound I of
Table 3 except that in compound 1 of Table 23, the compound has the general formula (IA) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 23 are
 
- 24 -
the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 23, the
compounds have the general formula (1A) where W and Z are CH and X and Y are N. Table 24
Table 24 consists of 662 compounds of the general formula (IA), where W and Z are
5 CH and X and Y are N, R is Cl, R' is 2,6-difluoro-4-methoxyphenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound I of Table 24 is the same as compound 1 of Table 4 except that in compound 1 of Table 24, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 24 are the same as compounds 2 to 662 of Table 4 except that in the compounds of Table 24, the
10 compounds have the general formula (I A) where W and Z are CH and X and Y are N. Table 25
Table 25 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is CI, RI is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 25 is the same as compound 1 of Table 5
15 except that in compound 1 of Table 25, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 25 are the same as compounds 2 to 662 of Table S except that in the compounds of Table 25, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.
Table 26
20    Table 26 consists of 662 compounds of the general formula (1A), where W and X are
CH and Y and Z are N, R is CI, R1 is 2,4,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 26 is the same as compound 1 of Table 1
except that in compound 1 of Table 26, the compound has the general formula (1 A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 26 are the same as
25 compounds 2 to 662 of Table 1 except that in the compounds of Table 26, the compounds have the general formula (IA) where W and X are CH and Y and Z are N.
Table 27
Table 27 consists of 662 compounds of the general formula (IA), where W and X are CH and Y and Z are N, R is Cl, R' is 2,5,6-trifluorophenyl, and the values of R3 and R4 are
30    as listed in Table 1. Thus, compound I of Table 27 is the same as compound 1 of Table 2
except that in compound 1 of Table 27, the compound has the general formula (I A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 27 are the same as
 
- 25 -
compounds 2 to 662 of Table 2 except that in the compounds of Table 27, the compounds have the general formula (1 A) where W and X are CH and Y and Z are N.
Table 28
Table 28 consists of 662 compounds of the general formula (I A), where W and X are
    5    CH and Y and Z are N, R is Cl, RI is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and
R4 are as listed in Table 1. Thus, compound 1 of Table 28 is the same as compound 1 of Table 3 except that in compound I of Table 28, the compound has the general formula (1A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 28 are the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 28, the
10 compounds have the general formula (1 A) where W and X are CH and Y and Z are N. Table 29
Table 29 consists of 662 compounds of the general formula (1A), where W and X are CH and Y and Z are N, R is Cl, RI is 2,6-difluoro-4-methoxyphenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 29 is the same as compound I of
15 Table 4 except that in compound 1 of Table 29, the compound has the general formula (IA) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 29 are the same as compounds 2 to 662 of Table 4 except that in the compounds of Table 29, the
compounds have the general formula (1A) where W and X are CH and Y and Z are N. Table 30
    20    Table 30 consists of 662 compounds of the general formula (1A), where W and X are
CH and Y and Z are N, R is Cl, RI is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 30 is the same as compound 1 of Table 5 except that in compound 1 of Table 30, the compound has the general formula (1A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 30 are the same as
25 compounds 2 to 662 of Table 5 except that in the compounds of Table 30, the compounds have the general formula ( I A) where W and X are CH and Y and Z are N.
Table 31
Table 31 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
 30 as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 31 R' is 2.6-difluorophenyl instead of 2-fluoro-6-chiorophenyl.
 
-26-
Table 32
Table 32 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
    5    same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 32 R1 is 2-fluorophenyl instead of 2-fluoro-6-chlorophenyl.
Table 33
Table 33 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
10 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 33 R' is 2,3,5,6-tetrafluorophenyl instead of 2-fluoro-6-chlorophenyl.
15 Table 34
Table 34 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
    20    exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 34 R' is 2-chloro-4,6-difluorophenyl instead of 2-fluoro-6-chloro¬phenyl.
Table 35
Table 35 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
 25 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds I to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 35 R' is 2-chlorophenyl instead of 2-fluoro-6-chlorophenyl.
30 Table 36
Table 36 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds I to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
 
-27-
same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds Ito 662 of Table 30 respectively, except that in all of the
compounds of Table 36 RI is 2,6-dichiorophenyl instead of 2-fluoro-6-chlorophenyl. Table 37
    5    Table 37 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds Ito 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds I to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
    10    compounds of Table 37 RI is 2,4-dichiorophenyl instead of 2-fluoro-6-chlorophenyl.
Table 38
Table 38 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
15 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 38 RI is 2,4,6-trichlorophenyl instead of 2-fluoro-6-chlorophenyl. Table 39
Table 39 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
20 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 39 R' is 2,3,6-trichlorophenyl instead of 2-fluoro-6-chlorophenyl.
25 Table 40
Table 40 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds Ito 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
    30    exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 40 RI is pentachlorophenyl instead of 2-fluoro-6-chlorophenyl.
 
- 28 -
Table 41
Table 41 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds I to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
5 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 41 RI is 2-fluoro-4,6-dichlorophenyl instead of 2-fluoro-6-chloro¬phenyl.
Table 42
10    Table 42 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
15    compounds of Table 42 R' is 4-fluoro-2,6-dichlorophenyl instead of 2-fluoro-6-chloro-
phenyl.
Table 43
Table 43 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds I to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
20 as compounds Ito 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 43 RI is 2-bromophenyl instead of 2-fluoro-6-chlorophenyl.
Table 44
25    Table 44 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds Ito 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
30        compounds of Table 44 RI is 2-fluoro-6-bromophenyl instead of 2-fluoro-6-chlorophenyl.
Table 45
Table 45 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
 
- 29-
as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 45 R' is 2-bromo-4,6-difluorophenyl instead of 2-fluoro-6-chloro-
    5    phenyl.
Table 46
Table 46 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
 10 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 46 R' is 2-fluoro-6-methylphenyl instead of 2-fluoro-6-chlorophenyl. Table 47
Table 47 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
 15 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 47 R' is 2-chloro-6-methylphenyl instead of 2-fluoro-6-chlorophenyl.
20 Table 48
Table 48 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
    25    exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 48 R' is 2-methoxyphenyl instead of 2-fluoro-6-chlorophenyl.
Table 49
Table 49 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
 30 as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds Ito 662 of Table 30 respectively, except that in all of the compounds of Table 49 RI is 2,6-dimethoxyphenyl instead of 2-fluoro-6-chlorophenyl.
 
- 30 -
Table 50
Table 50 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds I to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
    5    same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 50 R' is 2-fluoro-6-methoxyphenyl instead of 2-fluoro-6-chlorophenyl. Table 51
Table 51 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
10 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 51 R' is 2-trifluoromethylphenyl instead of 2-fluoro-6-chlorophenyl.
    15    Table 52
Table 52 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are
    20    exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 52 R' is 2-fluoro-6-trifluoromethylphenyl instead of 2-fluoro-6-chloro-phenyl.
Table 53
Table 53 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
    25    compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
as compounds I to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 53 R' is 2,6-di-(trifluoromethyl)phenyl instead of 2-fluoro-6-chloro-
    30    phenyl.
Table 54
Table 54 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
 
- 31 -
as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 54 RI is 2-chloro-6-trifluoromethylphenyl instead of 2-fluoro-6-
    5    chlorophenyl.
Table 55
Table 55 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
10 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 55 121 is 2,4-difluoro-6-trifluoromethylphenyl instead of 2-fluoro-6- chlorophenyl.
Table 56
    15    Table 56 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
    20    compounds of Table 56 R' is 2,4-difluoro-6-methoxyphenyl instead of 2-fluoro-6-chloro-
phenyl.
Table 57
Table 57 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds I to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
 25 as compounds Ito 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds I to 662 of Table 30 respectively, except that in all of the compounds of Table 57 R' is 2,4-difluoro-6-methylphenyl instead of 2-fluoro-6-chloro¬phenyl.
30 Table 58
Table 58 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respect ively, compounds 2649 to 3310 are exactly the
 
- 32 -
same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 58 R' is 2,4-difluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 59
5    Table 59 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
10        compounds of Table 59 RI is 3,5-difluoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.
Table 60
Table 60 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
15 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 60 RI is tetrafluoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 61
Table 61 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
20 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 61 RI is 3-fluoropyrid-2-yl instead of 2-fluoro-6-chlorophenyl.
25 Table 62
Table 62 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
30        exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 62 RI is 4-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.
 
- 33 -
Table 63
Table 63 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds Ito 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds Ito 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
5 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 63 R' is 3-fluoropyrid-4-y1 instead of 2-fluoro-6-chlorophenyl. Table 64
Table 64 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
10 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds I to 662 of Table 30 respectively, except that in all of the compounds of Table 64 R' is 2-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.
15 Table 65
Table 65 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are
20 exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 65 R' is 2,4,6-trifluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 66
Table 66 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
25 as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds I to 662 of Table 30 respectively, except that in all of the compounds of Table 66 R' is 3,5-difluoropyrid-2-y1 instead of 2-fluoro-6-chlorophenyl. Table 67
30    Table 67 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
 
-34-
exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 67 R' is 2,6-difluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 68
Table 68 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
5 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds I to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 68 R' is 2,4-difluoro-6-methoxypyrid-3-yl instead of 2-fluoro-6-chloro-
10    phenyl.
Table 69
Table 69 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
15 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 69 R' is 2-fluoro-4-chloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 70
Table 70 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
20 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 70 RI is 3-fluoro-5-chloropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.
25 Table 71
Table 71 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
30        exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 71 R' is 2-chloro-4-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.
 
-35-
Table 72
Table 72 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
5 same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 72 le is 2,4-dichloropyrid-3-y1 instead of 2-fluoro-6-chlorophenyl. Table 73
Table 73 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
10 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 73 le is 3-chloropyrid-2-yl instead of 2-fluoro-6-chlorophenyl.
15 Table 74
Table 74 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
20 exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 74 le is 4-chloropyrid-3-y1 instead of 2-fluoro-6-chlorophenyl. Table 75
Table 75 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325-to 1986 are exactly the same
25    as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 75 le is 3-chloropyrid-4-y1 instead of 2-fluoro-6-chlorophenyl. Table 76
30    Table 76 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds I to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
 
-36-
exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 76 R' is 2-chloropyrid-3-y1 instead of 2-fluoro-6-chlorophenyl. Table 77
Table 77 consists of 2648 compounds. Compounds I to 662 are exactly the same as
5 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 77 R' is 3-trifluoromethylpyrid-2-yl instead of 2-fluoro-6-chlorophenyl.
10 Table 78
Table 78 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to-1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
15 exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 78 R' is 4-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 79
Table 79 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
20 as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 79 R' is 3,5-dichloropyrid-2-yl instead of 2-fluoro-6-chlorophenyl. Table 80
25    Table 80 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds I to 662 of Table 30 respectively, except that in all of the
30        compounds of Table 80 R' is 4,6-dichloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.
Table 81
Table 81 consists of 2648 compounds. Compounds I to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
 
- 37 -
as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 331 Ito 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 81 R' is 3-trifluoromethylpyrid-4-y1 instead of 2-fluoro-6-chlorophenyl.
5 Table 82
Table 82 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
10    exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 82 R' is 2-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 83
Table 83 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
15 as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 83 R' is 2-fluoro-4-trifluoromethylpyrid-3-yl instead of 2-fluoro-6- chlorophenyl.
20 Table 84
Table 84 consists of 2648 compounds. Compounds I to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
25 exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 84 R' is 3-fluoro-5-trifluoromethylpyrid-4-y1 instead of 2-fluoro-6- chlorophenyl.
Table 85
Table 85 consists of 2648 compounds. Compounds I to 662 are exactly the same as
30 compounds Ito 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
 
- 38 -
compounds of Table 85 R' is 4-fluoro-2-trifluoromethylpyrid-3-y1 instead of 2-fluoro-6- chlorophenyl.
Table 86
Table 86 consists of 2648 compounds. Compounds I to 662 are exactly the same as
 5 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 86 RI is 2,6-dichloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.
10 Table 87
Table 87 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds Ito 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
 15 exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 87 R' is 3,5-dichloropyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 88
Table 88 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
20 as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 88 R' is 3-chloro-6-trifluoromethylpyrid-2-yl instead of 2-fluoro-6- chlorophenyl.
25 Table 89
Table 89 consists of 2648 compounds. Compounds I to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
 30 exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 89 R' is 3-fluoro-6-trifluoromethylpyrid-2-y1 instead of 2-fluoro-6- chlorophenyl.
 
- 39 -
Table 90
Table 90 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
5    same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are
exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 90 RI is pyrid-2-yl instead of 2-fluoro-6-chlorophenyl.
Table 91
Table 91 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
10 compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 91 R' is pyrid-3-y1 instead of 2-fluoro-6-chlorophenyl.
15 Table 92
Table 92 consists of 2648 compounds. Compounds I to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
20        exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 92 R1 is pyrid-4-yl instead of 2-fluoro-6-chlorophenyl.
Table 93
Table 93 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
25    as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 93 R' is 3-fluorothien-2-y1 instead of 2-fluoro-6-chlorophenyl. Table 94
30    Table 94 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds I to 662 of Table 25 respectively, and compounds 3311 to 3972 are
 
-40-
exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 94 RI is 3-chlorothien-2-yl instead of 2-fluoro-6-chlorophenyl. Table 95
Table 95 consists of 2648 compounds. Compounds I to 662 are exactly the same as
    5    compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 95 R' is 2,4-difluorothien-3-yl instead of 2-fluoro-6-chlorophenyl.
10 Table 96
Table 96 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
    15    exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 96 RI is 2,4-dichlorothien-3-yl instead of 2-fluoro-6-chlorophenyl. Table 97
Table 97 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
20 as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table RI is 2,4,5-trichlorothien-3-yl instead of 2-fluoro-6-chlorophenyl. Table 98
    25    Table 98 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
    30    compounds of Table 98 R' is piperidino instead of 2-fluoro-6-chlorophenyl.
Table 99
Table 99 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds Ito 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
 
-41-
as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 99 Ri is 2-methylpiperidino instead of 2-fluoro-6-chlorophenyl.
5 Table 100
Table 100 consists of 2648 compounds. Compounds I to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
10 exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 100 R' is 2,6-dimethylpiperidino instead of 2-fluoro-6-chlorophenyl. Table 101
Table 101 consists of 2648 compounds. Compounds I to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same
15    as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the
same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 101 R' is morpholino instead of 2-fluoro-6-chlorophenyl.
Table 102
20    Table 102 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
25        compounds of Table 102 RI is 2,6-dimethylmorpholino instead of 2-fluoro-6-chlorophenyl.
Table 103
Table 103 consists of 201,248 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables I to 102 (thus, for example, compound I of Table 103 is the same as compound 1 of Table 1, compound 663 of Table 103 is the same as
30    compound 1 of Table 2, compound 19,861 of Table 103 is the same as compound 1 of Table
31, compound 305,844 of Table 103 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 103 R is F instead of Cl.
 
- 42 -
Table 104
Table 104 consists of 201,248 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 104 is the same as compound 1 of Table 1, compound 663 of Table 104 is the same as
5 compound 1 of Table 2, compound 19,861 of Table 104 is the same as compound 1 of Table 31, compound 305,844 of Table 104 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 104 R is Br instead of Cl.
Table 109
Table 109 consists of 3310 compounds. Each of these compounds is exactly the same 10 as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table
109 is the same as compound 1 of Table 1, compound 663 of Table 109 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 109 X is CF instead of CH.
Table 110
15    Table 110 consists of 3310c compounds. Each of these compounds is exactly the
same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 110 is the same as compound 1 of Table 1, compound 663 of Table 110 is the same as
compound 1 of Table 2, etc.) except that in all of the compounds of Table 110 X is CC1 instead of CH.
20    Table 111
Table 111 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table
111 is the same as compound 1 of Table 1, compound 663 of Table 111 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 111 X is CBr
25    instead of CH.
Table 112
Table 112 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table
112 is the same as compound 1 of Table 1, compound 663 of Table 112 is the same as
30    compound 1 of Table 2, etc.) except that in all of the compounds of Table 112 X is CCH3
instead of CH.
 
- 43 -
Table 113
Table 113 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table
113 is the same as compound 1 of Table 1, compound 663 of Table 113 is the same as
5        compound 1 of Table 2, etc.) except that in all of the compounds of Table 113 Y is CF
instead of CH.
Table 114
Table 114 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table
10 114 is the same as compound 1 of Table 1, compound 663 of Table 114 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 114 Y is CCI instead of CH.
Table 115
Table 115 consists of 3310 compounds. Each of these compounds is exactly the same 15    as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table
115 is the same as compound 1 of Table 1, compound 663 of Table 115 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 115 Y is CBr instead of CH.
Table 116
20    Table 116 consists of 3310 compounds. Each of these compounds is exactly the same
as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table
116 is the same as compound 1 of Table 1, compound 663 of Table 116 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 116 Y is CCH3 instead of CH.
25
Compounds of formula (7) or (8), which are examples of compounds of general formula (I) where one of R and R2 is NR3R4, can be made as shown in Scheme 1, in which W, X, Y, Z, R', R3 and R4 have the meanings given above and R7 is C 1 at alkyl.
 
Scheme 1
i
,W'N    R7    OH
X    0    (3)    ,W    Base, e.g. NaH    _W
II    X    X_
II    II
Y., --,;-,,,,
Z    NH2
coupling method
H
amide    Y-,Z---NlRT solvent    Y
e.g. DMF
e.g.(1) SOCl2    0
(2) Et3N, CH2Cl2    (4)
CI
Y,    ,R3
Z N N
14
(8)
Compounds of general formula (4) can be prepared from compounds of general formula (2), which are either commercially available or made by methods known in the literature, by reaction with acids of general formula (3), using standard coupling methods, for
5    example by conversion to the acid chloride using a chlorinating agent such as thionyl
chloride, followed by reaction of the resultant acid chloride optionally in the presence of a base such as triethylamine, in a suitable solvent such as dichloromethane or toluene. Compounds of general formula (5) can be prepared by treating compounds of general formula (4) with a base such as sodium hydride, optionally in the presence of a Lewis acid
10 such as magnesium oxide, in a suitable solvent such as N,N-dimethylformamide (DMF) or toluene, at between room temperature and 150°C, but preferably at 60-90°C. Compounds of general formula (6) can be prepared by reaction of compounds of general formula (5) with a chlorination reagent such as phosphorus oxychloride, either neat or in a suitable solvent such as toluene, at between 50 and 150°C, but preferably between 80 and 110°C, or in a
15    microwave reactor at between 150 and 300°C, but preferably between 200 and 250°C.
Compounds of formula (7) and (8) can be prepared by reaction of compounds of general formula (6) with an amine R3R4NH, either neat, or in a suitable solvent such as DMF,
 
- 45 -
between room temperature and 150°C, but preferably between 50 and 80°C. If compounds
(7)    and (8) are produced as a mixture they can be separated by suitable means such as crystallisation or chromatography under normal or reverse phase conditions.
Compounds of the general formulae (5), (6), (7) and (8) may be derivatised, via the
5 chloro or hydroxy substituents, using routine chemical techniques to form other compounds of the general formula (1). Alternatively, other compounds of the general formula (1) may be prepared using a similar methodology to that described for preparing the compounds (5) to
(8)    and employing preparative techniques known from the chemical literature. Compounds of formula (7) can also be made as shown in Scheme 2.
10
Scheme 2
 

 
NH2
chlorinating    reductive
agent    X,WR    amination    X'W
II    II
e.g. POCI3    Y,    /    Y, ,j•,, .-
Z    N    CI    or alkylation    Z    N    Cl
(12)    (7)
Compounds of general formula (10) can be prepared from compounds of general formula (9), which are either commercially available or made by methods known in the literature, by reaction with acids of general formula (3), using standard coupling methods, for
15    example by conversion to the acid chloride using a chlorinating agent such as thionyl
chloride, followed by reaction of the resultant acid chloride optionally in the presence of a base such as triethylamine, in a suitable solvent such as dichloromethane or toluene.
Compounds of general formula (11) can be prepared by treating compounds of general formula (10) with a base such as sodium hydride, optionally in the presence of a Lewis acid
20 such as magnesium oxide, in a suitable solvent such as NN-dimethylformamide (DMF) or toluene, at between room temperature and 150°C, but preferably at 60-90°C. Compounds of
 
-46-
general formula (12) can be prepared by reaction of compounds of general formula (11) with a chlorination reagent such as phosphorus oxychloride, either neat or in a suitable solvent
such as toluene, at between 50 and 150°C, but preferably between 80 and 110°C, or in a microwave reactor at between 150 and 300°C, but preferably between 200 and 250°C.
5 Compounds of formula (7) can be prepared from compounds of formula (12) by reductive amination, for example by reaction with a ketone or aldehyde in a suitable solvent such as ethanol or toluene, at between room temperature and reflux, optionally in the presence of an acid catalyst such as para-toluenesulphonic acid or a drying agent such as molecular sieves, followed by treatment with a suitable reducing agent such as sodium borohydride, at between
10 —20°C and 40°C, but preferably at room temperature. The aldehyde or ketone is chosen so that the desired groups R3 and R4 are formed after reduction of the product of reaction with the amine (12). For example if compounds of formula (12) are reacted with one equivalent of propionaldehyde and then sodium borohydride, compounds of formula (7) where R3 is n-
propyl, and R4 is hydrogen are formed. If required, the reaction can be repeated with a
15    different aldehyde or ketone. For example, if acetone is used for the second reaction, then
compounds of formula (7) where R3 is n-propyl and R4 is iso-propyl, are formed. Alternatively compounds of formula (7) can be formed from compounds of formula (12) by alkylation with a group R3LG, by treatment with a suitable base such as sodium hydride in a solvent such as DMF, or a base such as potassium carbonate in a solvent such as acetone or
20 DMF, at between —78°C and 100°C, but preferably between room temperature and 60°C,
followed by treatment with R4LG in a second step under the same conditions if required.
Scheme 3
 

 
(6)    (13)
 

 
( 1 4 )    (15)
 
- 47 -
Compounds of formula (13) can be prepared as shown in Scheme 3 from compounds
of formula (6) by reaction with a source of fluoride ion, such as potassium fluoride, in a suitable solvent such as sulpholane, at a temperature between 50°C and 200°C, but preferably at 80-150°C. Compounds of formula (14) and/or compounds of formula (15) can be prepared
5    from difluoro compounds of formula (13) by reaction with an amine of formula R3R4NH in a
suitable solvent such as DMF or CH2C12, at a temperature of 0°C-100°C, but preferably at room temperature.
Scheme 4
R    1:13
MHaRsolvent
e.g. CuBr/DMF
X"-
it    II
y,Y Hal'    R`N-R3
     
(16)    (17)

Compounds of general formula (16), where Hal' is chlorine or fluorine, can be
10 converted into compounds of formula (17) as shown in Scheme 4. Compounds of general
formula (17) where Hale is bromine or iodine can be formed by reacting compounds of general formula (16) with a metal halide, for example cuprous bromide, in a suitable solvent, for example DMF, at between room temperature and 155°C, but preferably between 70°C and 155°C.
15    Further assistance in the preparation of the compounds of formula (1) may be derived
from the following publications: Emilio, Toja, et. al., J. Heterocyclic Chem., 23, 1955 (1986), H. Schafer, et. al., J. f prakt. Chemie, 321(4), 695 (1970) and H. Bredereck et. aL, Chem. Ber. 96, 1868-1872 (1993).
The intermediate chemicals having the general formulae (4), (5), (6) and (13): 0    OH    CI
 
X,W
X,W
,W
II    II    II
Z    Y,Z N CI    Z N
(5)    (6)    (13)
 
wherein W, X, Y, Z, RI and R7 are as define above, other than the compound of formula (6) wherein X and Y are N, W and Z are C-Cl and RI is Cl, are believed to be novel compounds and form a further part of this invention.
It should be noted that the intermediate of general formula (5) may exist in the 25    tautomeric forms (a), (b) and (c) as well as in the form shown in formula (5):
 
The invention as defined by the general formula (5) embraces all such tautomers.
Of particular interest are the intermediates listed in Tables 128 to 132 below. In Table
128 the compounds have the general formula (4) where R7 is methyl and W, X, Y, Z and RI
5    have the values shown in the table.
Table 128
Cmpd No.    RI    W    X,    Y    Z
1    2,4,6-trifluorophenyl    N    CH    CH    N
2    2,5,6-trifluorophenyl    N    CH    CH    N
3    2,3,4,5,6-pentafluorophenyl    N    CH    CH    N
4    2,3,5,6-tetrafluorophenyl    N    CH    CH    N
5    2,6-difluoro-4-methoxyphenyl    N    CH    CH    N
6    2-fluoro-6-chlorophenyl    N    CH    CH    N
7    2,6-difluorophenyl    N    CH    CH    N
8    2,3,5,6-tetrafluorophenyl    N    CH    CH    N
9    2-fluorophenyl    N    CH    CH    N
10    2-chlorophenyl    N    CH    CH    N
11    2-bromophenyl    N    CH    CH    N
12    2 ,4 -dichlorophenyl    N    CH    CH    N
13    2,4,6-trifluorophenyl    N    N    CH    CH
14    2,5,6-trifluorophenyl    N    N    CH    CH
15    2,3,4,5,6-pentafluorophenyl    N    N    CH    CH
16    2,3,5,6-tetrafluorophenyl    N    N    CH    CH
17    2,6-difluoro-4-methoxyphenyl    N    N    CH    CH
18    2-fluoro-6-chlorophenyl    N    N    CH    CH
19    2,6-difluorophenyl    N    N    CH    CH
 
- 49 -
20    2,3,5,6 -tetraflu orophenyl    N    N    CH    CH
21    2- fluoropheny 1    N    N    CH    CH
22    2-chlorophenyl    N    N    CH    CH
23    2-bromophenyl    N    N    CH    CH
24    2,4-dichlorophenyl    N    N    CH    CH
25    2,4,6-trifluorophenyl    CH    N    N    CH
26    2,5,6-trifluorophenyl    CH    N    N    CH
27    2,3,4,5,6-pentafluorophenyl    CH    N    N    CH
28    2,3,5,6-tetrafluorophenyl    CH    N    N    CH
29    2,6-difluoro-4-methoxyphenyl    CH    N    N    CH
30    2-fluoro-6-chlorophenyl    CH    N    N    CH
31    2,6-difluorophenyl    CH    N    N    CH
32    2,3,5,6-tetrafluorophenyl    CH    N    N    CH
33    2-fluorophenyl    CH    N    N    CH
34    2-chlorophenyl    CH    N    N    CH
35    2-bromophenyl    CH    N    N    CH
36    2,4-dichlorophenyl    CH    N    N    CH
37    2,4,6-trifluorophenyl    CH    CH    N    N
38    2,5,6-trifluorophenyl    CH    CH    N    N
39    2,3,4,5,6-pentafluorophenyl    CH    CH    N    N
40    2,3,5,6-tetrafluorophenyl    CH    CH    N    N
41    2,6-difluoro-4-methoxyphenyl    CH    CH    N    N
42    2-fluoro-6-chlorophenyl    CH    CH    N    N
43    2,6-difluorophenyl    CH    CH    N    N
44    2,3,5,6-tetrafluorophenyl    CH    CH    N    N
45    2-fluorophenyl    CH    CH    N    N
46    2-chlorophenyl    CH    CH    N    N
47    2-bromophenyl    CH    CH    N    N
48    2,4-dichlorophenyl    CH    CH    N    N
 
- 50 -
Table 129
Table 129 consists of 48 compounds of the general formula (5), where W, X, Y, Z and RI have the values given in Table 128. Thus, compound 1 of Table 129 has the same W. X, Y, Z and R' values as compound 1 of Table 128, etc.
    5    Table 130
Table 130 consists of 48 compounds of the general formula (6), where W, X, Y, Z and R1 have the values given in Table 128. Thus, compound 1 of Table 130 has the same W, X, Y, Z and RI values as compound 1 of Table 128, etc.
Table 131
    10    Table 131 consists of 48 compounds of the general formula (13), where W, X, Y, Z
and RI have the values given in Table 128. Thus, compound 1 of Table 131 has the same W, X, Y, Z and R' values as compound 1 of Table 128, etc.
Table 132
Table 132 consists of 48 compounds of the general formula (4), where W, X, Y, Z
    15    and R' have the values given in Table 128 and R7 is ethyl. Thus, compound 1 of Table 132 is
the same as compound 1 of Table 128 except that in compound 1 of Table 132, R7 is ethyl instead of methyl. Similarly, compounds 2 to 48 of Table 132 are the same as compounds 2 to 48 of Table 128 except that in the compounds of Table 132, R7 is ethyl.
The compounds of formula (1) are active fungicides and may be used to control one
20 or more of the following pathogens: Pyricularia oryzae (Magnaporthe grisea) on rice and wheat and other Pyricularia spp. on other hosts; Puccinia triticina (or recondita), Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts (for example turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants); Erysiphe cichoracearum on cucurbits (for example
    25    melon); Blumeria (or Erysiphe) graminis (powdery mildew) on barley, wheat, rye and turf
and other powdery mildews on various hosts, such as Sphaerotheca macularis on hops, Sphaerotheca fusca (Sphaerotheca fuliginea) on cucurbits (for example cucumber), Leveillula taurica on tomatoes, aubergine and green pepper, Podosphaera leucotricha on apples and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp.,
30 Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Mycosphaerella graminicola (Septoria tritici) and Phaeosphaeria nodorum (Stagonospora nodorum or Septoria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (for example wheat, barley, rye), turf and other hosts; Cercospora arachidicola and
 
- 51 -
Cercosporidium personatum on peanuts and other Cercospora spp. on other hosts, for example sugar beet, bananas, soya beans and rice; Botrytis cinerea (grey mould) on
tomatoes, strawberries, vegetables, vines and other hosts and other Botrytis spp. on other hosts; Alternaria spp on vegetables (for example carrots), oil-seed rape, apples, tomatoes,
5    potatoes, cereals (for example wheat) and other hosts; Venturia spp_ (including Venturia
inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (for example wheat) and tomatoes; Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat, cucurbits and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts;
10 Aspergillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochyta spp. on peas, wheat, barley and other hosts; Stemphylium spp. (Pleospora spp.) on apples, pears, onions and other hosts; summer diseases (for example bitter rot (Glomerella cingulata), black rot or frogeye leaf spot (Botryosphaeria obtusa), Brooks fruit spot (Mycosphaerella pomi), Cedar apple rust (Gymnosporangium juniperi-virginianae), sooty blotch (Gloeodes
15 pomigena), flyspeck (Schizothyrium pomi) and white rot (Botryosphaeria dothidea)) on
apples and pears; Plasmopara viticola on vines; other downy mildews, such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. (including Pythium ultimum) on turf and other hosts; Phytophthora infestans on potatoes
20    and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper,
ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris on rice and turf and other Rhizoctonia spp. on various hosts such as wheat and barley, peanuts, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, potatoes, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Gibberella fujikuroi on rice; Colletotrichum spp. on a
25        range of hosts including turf, coffee and vegetables; Laetisaria fucifonnis on turf;
Mycosphaerella spp. on bananas, peanuts, citrus, pecans, papaya and other hosts; Diaporthe
spp. on citrus, soybean, melon, pears, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Verticillium spp. on a range of hosts including hops, potatoes and tomatoes; Pyrenopeziza spp. on oil-seed rape and other hosts; Oncobasidium
30        theobromae on cocoa causing vascular streak dieback; Fusariurn spp., Typhula spp.,
Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp. and Claviceps purpurea on
a variety of hosts but particularly wheat, barley, turf and maize; Ramulana spp. on sugar beet, barley and other hosts; post-harvest diseases particularly of fruit (for example
 
-52-
Penicillium digitatum, Penicillium italicum and Trichoderma viride on oranges,
Colletotrichum musae and Gloeosporium musarum on bananas and Botrytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidxellii, Phellinus igniarus, Phornopsis viticola, Pseudopeziza tracheiphila and Stereum hirsutum; other
5 pathogens on trees (for example Lophodermium seditiosum) or lumber, notably Cephaloascus fragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp.,
Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and A ureobasidiurn pullulans; and fungal vectors of viral diseases (for example Polymyxa graminis on cereals as the vector of barley yellow mosaic
10 virus (BYMV) and Polymyxa betae on sugar beet as the vector of rhizomania).
A compound of formula (I) may move acropetally, basipetally or locally in plant tissue to be active against one or more fungi. Moreover, a compound of formula (1) may be
volatile enough to be active in the vapour phase against one or more fungi on the plant.
The invention therefore provides a method of combating or controlling phytopatho-
15 genic fungi which comprises applying a fungicidally effective amount of a compound of formula (1), or a composition containing a compound of formula (1), to a plant, to a seed of a
plant, to the locus of the plant or seed or to soil or any other plant growth medium, e.g. nutrient solution.
The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the 20    fungicidal method of the invention includes protectant, curative, systemic, eradicant and
antisporulant treatments.
The compounds of formula (1) are preferably used for agricultural, horticultural and turfgrass purposes in the form of a composition.
In order to apply a compound of formula (1) to a plant, to a seed of a plant, to the
25    locus of the plant or seed or to soil or any other growth medium, a compound of formula (1)
is usually formulated into a composition which includes, in addition to the compound of formula (I), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA).
SFAs are chemicals that are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and
30 thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (1). The composition is generally used for the control of fungi such that a
 
- 53 -
compound of formula (1) is applied at a rate of from 0.1 g to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to lkg per hectare.
When used in a seed dressing, a compound of formula (1) is used at a rate of 0.0001g to lOg (for example 0.001g or 0.05g), preferably 0.005g to 10g, more preferably 0.005g to
5    4g, per kilogram of seed.
In another aspect the present invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of formula (1) and a suitable carrier or diluent therefor.
In a still further aspect the invention provides a method of combating and controlling
10    fungi at a locus, which comprises treating the fungi, or the locus of the fungi with a
fungicidally effective amount of a composition comprising a compound of formula (1).
The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble
15    concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable
concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (E0)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged
20    and the physical, chemical and biological properties of the compound of formula (1).
Dustable powders (DP) may be prepared by mixing a compound of formula (1) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite,
alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur;- lime, flours, talc and other organic and
25    inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
Soluble powders (SP) may be prepared by mixing a compound of formula (1) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of
30        said agents to improve water dispersibility/solubility. The mixture is then ground to a fine
powder. Similar compositions may also be granulated to form water soluble granules (SG).
Wettable powders (WP) may be prepared by mixing a compound of formula (1) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or
 
- 54 -
more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound of
5 formula ( I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (1) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (1) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates,
10    mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are
commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting
15    agent or dispersing agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of
formula (1) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These
solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).
20    Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by
dissolving a compound of formula (1) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200;
25    SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclo-
hexanone), alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyr¬rolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty
acids (such as C8-C10 fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with
30 sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (1) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid
 
-55-
or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents that have a low solubility in water.
5    Microemulsions (ME) may be prepared by mixing water with a blend of one or more
solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (I) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil
10 system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An
ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of
15 finely divided insoluble solid particles of a compound of formula (1). SCs may be prepared by ball or bead milling the solid compound of formula (1) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of
20        formula (1) may be dry milled and added to water, containing agents hereinbefore described,
to produce the desired end product.
Aerosol formulations comprise a compound of formula (1) and a suitable propellant (for example n-butane). A compound of formula (1) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to
25    provide compositions for use in non-pressurised, hand-actuated spray pumps.
A compound of formula (1) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
Capsule suspensions (CS) may be prepared in a manner similar to the preparation of
30    EW formulations but with an additional polymerisation stage such that an aqueous dispersion
of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a
 
-56-
coacervation procedure. The compositions may provide for controlled release of the compound of formula (l) and they may be used for seed treatment. A compound of formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
5    A composition may include one or more additives to improve the biological
performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (1)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and
10 blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (1)).
A compound of formula (1) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid
15        composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension
(CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of,
respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).
20    Wetting agents, dispersing agents and emulsifying agents may be SFAs of the
cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic
25    monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated
aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecyl-benzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- and tri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate),
30 phosphate esters (products from the reaction between one or more fatty alcohols and phos¬phoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these
 
- 57 -
products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.
Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.
Suitable SFAs of the non-ionic type include condensation products of alkylene
5    oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with
fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as oetylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for
10        example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl
amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
15    A compound of formula (1) may be applied by any of the known means of applying
fungicidal compounds. For example, it may be applied, formulated or unformulated, to any
part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems),
20    directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste
formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
A compound of formula (1) may also be injected into plants or sprayed onto 25    vegetation using electrodynamic spraying techniques or other low volume methods, or
applied by land or aerial irrigation systems.
Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may
30 include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to
water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may
 
- 58 -
contain varying amounts of a compound of formula (1) (for example 0.000] to 10%, by weight) depending upon the purpose for which they are to be used.
A compound of formula (1) may be used in mixtures with fertilisers (for example
nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types
    5    include granules of fertiliser. The mixtures suitably contain up to 25% by weight of the
compound of formula (1).
The invention therefore also provides a fertiliser composition comprising a fertiliser and a compound of formula (1).
The compositions of this invention may contain other compounds having biological
 10 activity, for example micronutrients or compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
By including another fungicide, the resulting composition may have a broader
spectrum of activity or a greater level of intrinsic activity than the compound of formula (1)
    15    alone. Further the other fungicide may have a synergistic effect on the fungicidal activity of
the compound of formula (1).
The compound of formula (1) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional
    20    active ingredient may: provide a composition having a broader spectrum of activity or
increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of
formula (1); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility
    25    of the composition.
Examples of fungicidal compounds which may be included in the composition of the invention are AC 382042 (N-(1-cyano-1,2-dimethylpropy1)-2-(2,4-dichlorophenoxy) pro-pionamide), acibenzolar-S-methyl, alanycarb, aldimorph, anilazine, azaconazole, azafenidin,
azoxystrobin, benalaxyl, benomyl, benthiavalicarb, biloxazol, bitertanol, blasticidin S,
    30    boscalid (new name for nicobifen), bromuconazole, bupirimate, captafol, captan,
carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA 41396, CGA
41397, chinomethionate, chlorbenzthiazone, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper
 
-59-
sulphate, copper tallate, and Bordeaux mixture, cyamidazosulfamid, cyazofamid (11(F-916),
cyflufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb,
difenoconazole, difenzoquat, diflumetorim, 0,0-di-iso-propyl-S-benzyl thiophosphate,
5    dimefluazole, dimetconazole, dimethirimol, dimethomorph, dimoxystrobin, diniconazole,
dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethyl (Z)-N-benzyl-N(Emethyl(methyl-thioethylideneaminooxycarbonyDaminolthio)-13-alaninate, etridiazole, famoxadone,
fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil (AC 382042),
10        fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone,
fluazinam, fludioxonil, flumetover, flumorph, fluoroimide, fluoxastrobin, fluquinconazole,
flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione,
15        iprovalicarb, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl,
LY186054, LY211795, LY 248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil,
metalaxyl, metalaxyl M, metconazole, metiram, metiram-zinc, metominostrobin, metra¬fenone, MON65500 (N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide), myc-
lobutanil, NTNO301, neoasozin, nickel dimethyldithiocarbamate, nitrothale-isopropyl,
20    nuarimol, ofurace, organomercury compounds, orysastrobin, oxadixyl, oxasulfuron, oxolinic
acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosphorus acids, phthalide, picoxystrobin, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic
acid, proquinazid, prothioconazole, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil,
25    pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinomethionate,
quinoxyfen, quintozene, silthiofam (MON 65500), S-imazalil, simeconazole, sipconazole, sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamide, 2-(thiocyanomethylthio)-
benzothiazole, thiophanate-methyl, thiram, tiadinil, timibenconazole, tolclofos-methyl,
30    tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph,
trifloxystrobin, triflumizole, triforine, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb, ziram, zoxamide and compounds of the formulae:
 
- 60 -
 

 
The compounds of formula (1) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Some mixtures may comprise active ingredients, which have significantly different
5 physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension
10 (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.
The invention is illustrated by the following Examples in which the following abbreviations are used:
ml = millilitres    f = fine
g = grammes    THE = tetrahydrofuran
ppm = parts per million    DCM = dichloromethane
s = singlet    DMF = N, N-dimethylformamide
d = doublet    DMSO = dimethylsulphoxide
t = triplet    DMAP = 4-dimethylaminopyridine
q = quartet    NMR = nuclear magnetic resonance
m = multiplet    HPLC = high performance liquid
b = broad    chromatography
15
 
- 61 -
EXAMPLE I
This Example illustrates the preparation of [6-chloro-7-(2,4,6-trifluoropheny1)-pyrido[2,3- b]pyrazin-8-y1J-isopropylamine (Compound No. 3, Table 1).
CH3
 

 
5    Step 1
Methyl 2-amino-3-pyrazine carboxylate (2.2 g) was dissolved in dry DCM (20 ml) to give a cloudy pale yellow solution, and pyridine (2 ml) in dry DCM (12 ml) was added. The stirred suspension was cooled in an ice bath, and 2,4,6-trifluorophenylacetyl chloride (3.0 g) in dry DCM (13 ml) was added dropwise. The reaction gradually became a deep orange, and
10    then went clear. It was stirred for 6 hours and stood overnight. The reaction mixture was
washed with water, brine, and then dilute hydrochloric acid, and the DCM layer was dried over magnesium sulphate. The solvent was evaporated to yield an orange solid which was triturated with ether, to give methyl 2[2,4,6-trifluorophenylacetylamino1-3-pyrazine carboxylate as a yellow solid (1.5 g).
15    11-1 NMR (CDC13) 8 ppm: 4.03 (s,5H), 6.74 (t,2H), 8.43 (d,1H), 8.61 (d,1H) 10.9 (s,1H).
Step 2
The product of Step 1 (3.25 g) was dissolved in DMF (10m1) and added dropwise to a stirred suspension of sodium hydride (0.60 g of an 80% dispersion in mineral oil) in DMF (80 ml). There was an immediate reaction, and the mixture was stirred at room temperature
20 for 2 hours, and at 80°C for 8 hours. The reaction mixture was cooled and evaporated to give
a yellow solid (3 g), which was then acidified with dilute hydrochloric acid. The resultant white suspension was filtered and collected, washed with ether and dried to give 6,8- dihydroxy-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine (1.8 g).
NMR (d6-DMSO) 6 ppm: 7.25 (t,2H), 8.6 (fd,1H),8.7 (fd,1H), 12.6 (s,1H). 25    Step 3
The product from Step 2 (0.90 g) was added portion-wise to phosphorus oxychloride (10 ml) with stirring. The reaction was exothermic. The mixture became brown with a fine suspension, and was then refluxed for 6 hours. Excess phosphorus oxychloride was evaporated, the mixture was diluted with DCM, and then washed with water to give a black
 
- 62 -
oil, which was purified by flash column chromatography on silica gel (40-60) eluting with diethyl ether, to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine as a dark oil (0.40 g).
IH NMR (CDC13)45 ppm: 6.9 (t,2H), 9.1(d, I H), 9.2 (d,1 H).
5    Alternative procedure for Step 3
Phosphorus oxychloride (20.90 g) was added over 15 minutes to a suspension of the product from Step 2 (10.0 g), in l,2-dichloroethane (80 ml) containing DMF (5.0 g) maintained at a temperature between 79°- 81°C. Stirring was continued at this temperature for 3 hours, and the reaction was then cooled. The mixture was poured carefully into
10 saturated sodium bicarbonate solution (500 ml) keeping the temperature below 30 °C. After stirring for 20 minutes the product was extracted with ethyl acetate, washed with water and brine and dried over sodium sulphate. The solvent was evaporated to yield a dark red oil, which was purified by flash chromatography eluting with cyclohexane:ethyl acetate, 4:1 to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine as a light brown solid (7.5
15    g), m.p. 139-141 °C.
Step 4
The product from Step 3 (0.20 g), isopropylamine (1.0 ml) and N-ethyl-diisopropylamine (0.20 g) were refluxed in a sealed tube at 90°C for 17 hours. The dark coloured reaction mixture was evaporated to give an oil, which was purified by flash column chromatography
20    on silica gel (40-60) in diethyl ether.
A fraction containing a mixture of isomers (0.080 g), was obtained, and a portion of this mixture (0.020g) was purified by reverse phase HPLC on a Kromasil 100-5C18 column, eluting with methanol:water (65:35) to give (6-chloro-7-(2,4,6-trifluoropheny1)-pyrido[2,3- b}pyrazin-8-y11-isopropylamine as a frothy solid (0.013 g).
25H NMR (CDC13) 8 ppm: 1.1 (d,6H), 3.26 (m,1H), 6.84 (m,2H), 6.95 (bd,1H), 8.67 (d,1H), 9.0 (d, I H),
 
- 63 -
EXAMPLE 2
This Example illustrates the preparation of [6-fluoro-7-(2,4,6-trifluoropheny1)- pyrido[2,3-b]pyrazin-8-y11-isopropylamine (Compound No. 3, Table 103)
 
    5    Step 1
6,8-Dichloro-7-(2,4,6-trifluoropheny1)-pyrido[2,3-14yrazine (1.25 g) and potassium fluoride (0.66 g, spray dried) in dry sulpholane (5 ml) were heated to 130 °C for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was
washed with water and brine and dried over sodium sulphate. After evaporation of the
    10    solvent, the remaining oil was purified by flash chromatography on silica gel eluting with
cyclohexane:ethyl acetate, 3:1 to yield 6,8-difluoro-7-(2,4,6-trifluoropheny1)-pyrido[2,3-13]- pyrazine as a slightly brownish solid (0.79 g), m.p. 120-121 °C.
Step 2
The product from Step 1 (0.30 g) was added to a suspension of isopropylamine
15 (0.090 g), potassium carbonate (0.21 g) and a catalytic amount of DMAP in DMF (3 ml), and the mixture was stirred at room temperature for 19 hours. After addition of ethyl acetate, the
mixture was washed with water and brine, dried over sodium sulphate, filtered and the solvent evaporated. The residue was purified by flash chromatography eluting with toluene:ethyl acetate, 9:1 to give [6-fluoro-7-(2,4,6-trifluoropheny1)-pyrido[2,3-b]pyrazin-8-
    20    y11-isopropylamine as a yellow powder (0.20 g), m.p. 127-128 °C.
EXAMPLE 3
This Example illustrates the preparation of [6-chloro-7-(2,4,6-trifluoropheny1)-pyrido[3,2- Opyridazin-8-yThisopropylamine (Compound No. 3, Table 11) .
 

 
25    Step I
 
- 64 -
A solution of 4-aminopyridazine-3-carbonitrile (0.248 g, prepared as in J. Het. Chem.(1970), 3, 467-473) in absolute ethanol (30 ml)was saturated with hydrogen chloride gas, the flask being cooled in an ice bath. The ice bath was then removed and the resulting
solution was refluxed for 18 hours. It was then cooled, the solvent evaporated, and cold,
5    saturated aqueous sodium bicarbonate was added. The aqueous phase was then extracted
with DCM, the organic phases were combined, dried over magnesium sulphate, filtered and evaporated to give 4-aminopyridazine-3-carboxylic acid ethyl ester as a white solid (0.229g). The aqueous phase was evaporated, DCM was added, the organic phase was isolated, dried
over magnesium sulphate, filtered and evaporated under vacuo to give further ester as a
10    white solid (0.010 g), m.p. 149-150°C.
NMR (CDC13) 8 ppm: 1.48 (t,3H), 4.52 (q,2H), 6.73 (d,1H), 8.75 (d,1H).
Step 2
A mixture of the product from Step 1 (0.239 g) and DMAP (0.175 g) in dry toluene
(1 ml) was added to 2,4,6-trifluorophenylacetyl chloride (crude product from reaction of
15    0.275 g 2,4,6-trifluorophenylacetic acid and oxalyl chloride) and a few drops of DMF in
toluene (1 ml) at room temperature, giving a thick yellow precipitate. The stirred suspension was heated for 3 hours at reflux, becoming dark brown/green with a green precipitate. It was left to stand overnight for 18 hours. The solid was collected and washed with diethyl ether.
The dark green filtrate was evaporated to give a dark green liquid which was purified by
20 flash column chromatography on silica gel (40-60) eluting with ethyl acetate to give 442-(2,4,6-trifluoropheny1)-acetylaminol-pyridazine-3-carboxylic acid ethyl ester as green/yellow oil that solidified on standing (0.307 g).
NMR (CDC13) 8 ppm: 1.50 (t,3H), 3.87 (s,2H), 4.55 (q,2H), 6.77 (t,2H), 8.78 (d,1 H), 9.15 (d, 1 H), 11.20 (bs,1H).
25    Step 3
The product from Step 2 (0.307 g) and potassium carbonate (0.25 g) were stirred in dry DMF (I0 ml) at 110°C for 2 hours and then cooled and stood for 18 hours. The DMF
was evaporated and the resulting brown solid was triturated with diethyl ether and the organic phase decanted. The solid was dissolved in water then acidified with dilute
30    hydrochloric acid to neutrality. Most of the aqueous phase was then evaporated, leading to
precipitation of a black solid that was filtered, and the yellow/brown aqueous phase was evaporated to dryness, affording a residue that was dissolved in methanol, the insoluble inorganic salts were filtered and the organic phase was evaporated to dryness to give 7-
 
- 65 -
(2,4,6-trifluoropheny1)-5H-pyrido[3,2-c]pyridazine-6,8-dione as a light brown/beige solid (0.258 g).
11-1 NMR (CD3OD) 5 ppm: 6.83 (2d,2H), 7.44 (d,1H), 9.00 (d,1H).
Step 4
5    Phosphorus oxychloride (0.048 ml) was added to the product from Step 3 (0.05 g) in
1,2-dichloroethane (2 ml) containing a catalytic amount of DMF. The suspension was stirred and refluxed for 1 hour and then stood for 18 hours, and then refluxed for a further hour and then allowed to cool. The excess phosphorus oxychloride was evaporated to give a brown
oil, which was dissolved in DCM and washed with cold water. The organic layer was
10    separated and dried over magnesium sulphate, filtered and evaporated to give a brown oil,
which was purified by flash column chromatography on silica gel (40-60) eluting with diethyl ether to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazine as a yellow oil (0.015 g).
1H NMR (CDC13) 8 ppm: 6.92 (m,2H), 8.11 (d,1H), 9.71 (d,1H).
15    Step 5
Isopropylamine (0.5 ml) was added to the product from Step 4 (0.015 g) dissolved in DCM (1m1) containing dimethylacetamide (0.3 ml) in a sealed tube. The yellow solution became yellow/greenish. The vessel was then sealed and stirred at room temperature. The solvents were evaporated and the crude residue was purified using preparative thin layer
20    chromatography silica gel plates eluting with ethyl acetate:hexane 1:1 to give
[6-Chloro-7-(2,4,6-trifluoropheny1)-pyrido[3,2-c]pyridazin-8-y1J-isopropylamine (0.003 g). 'H NMR (CDCI3) S ppm: 1.16 (d,6H), 3.41 (m,1H), 6.85 (dd,2H), 7.79 (bs,1H), 7.84 (d,1H). 9.40 (d,1H).
EXAMPLE 4
25    This Example illustrates the preparation of [2-chloro-3-(2,4,6-trifluoropheny1)-pyrido[2,3-
d]pyridazin-4-y1]-isopropylamine (Compound No. 3, Table 21).
 
CH, H3CNHF N
N
CI
 
- 66 -
Step 1
5-Aminopyridazine-4-carboxylic acid ethyl ester (1.26 g, prepared according to J. Het. Chem., (1968), 5, 845) was dissolved in dry toluene (125 ml) at 90°C, and DMAP (0.92
g) was added. 2,4,6-Trifluorophenylacetyl chloride (1.75 g of 95% purity material) was
5    added dropwise with stirring at 70°C, and a white solid precipitated. The reaction was stirred
at reflux for 5 hours and then filtered hot. The filtrate was evaporated to give 54242,4,6- trifluoropheny1)-acetylamino1-pyridazine-4-carboxylic acid ethyl ester as a white solid (2.6 g), m.p. 143-144°C.
'H NMR (CDCI3) 8 ppm: 1.45 (t,3H), 3.90 (s,2H), (4.45 (q,2H), 6.75 (m,2H), 9.45 (s1H), 10    10.60 (s,1H), 11.1 (bs,1H).
Step 2
The product from Step 1 (2.5 g) was dissolved in dry THF (50 ml) and the flask purged with nitrogen. Sodium bis-trimethylsilylamide (22.1 ml of a 1M solution in THF) was added dropwise with stirring at 0°C. A yellow precipitate appeared, and the reaction was
15    stirred for 3 hours at 0°C. The reaction was quenched with concentrated hydrochloric acid (5
ml) at 0°C and then poured onto ice water, extracted with DCM and dried over magnesium sulphate. The solvent was evaporated to give 3-(2,4,6-trifluoropheny1)-1H-pyrido[2,3-
d]pyridazine-2,4-dione as a yellow solid. Further product crystallised out of the aqueous solution overnight, to give a total yield of 1.29 g, m.p. >300°C.
20    1H NMR (d6-DMSO) 8 ppm: 7.25 (m,2H), 9.17 (s,1H), 9.47 (s,1H), 12.30 (bs,1H).
Step 3
The product from Step 2 (0.10 g) was heated to 90°C with phosphorus oxychloride
(1.6 ml) with stirring. After 1 hour a clear yellow solution was obtained and the excess solvent was evaporated and ice water was added, giving a yellow solid. This was extracted
25    with DCM, and the solution dried over magnesium sulphate and evaporated to give 2,4-
dichloro-3-(2,4,6-trifluoropheny1)-pyrido[2,3-d]pyridazine as a yellow foamy glass (0.11 g). 1H NMR (CDC13) 8 ppm: 6.90 (m,2H), 9.80 (s,1H), 10.0 (s, H).
Step 4
Isopropylamine (1.5 ml) was added to the product from Step 3 (0.020 g) in DCM and
30    the tube stoppered and the reaction stirred overnight at room temperature. The DCM was
evaporated and water added to the residue, which was then extracted with DCM. The extract was dried over magnesium sulphate and evaporated to give an orange oil, which was purified by HPLC eluting with ethyl acetate:hexane 4:1 to give
 
- 67 -
[2-Chloro-3-(2,4,6-trifluoropheny1)-pyrido[2,3-d]pyridazin-4-y1J-isopropylamine (0.007 g) 1H NMR (CDC13) 8 ppm: 1.27 (d,6H), 4.05 (m,11-1), 4.90 (bs,1H), 6.92 (m,2H), 9.55 (s,11-1), 9.90 (s,1H).
EXAMPLE 5
5    This Example illustrates the preparation of [7-chloro-6-(2,4,6-trifluoropheny1)-pyrido[2,3-
c]pyridazin-5-y11-isopropylamine (Compound No. 3, Table 26).
3
H3C NHF
Compound No. 3, Table 26
N,
N    N    CI
Step 1
3-Aminopyridazine-4-carboxylic acid (1.68 g, prepared as in JOC, (1985), 50, 346)
10    was refluxed in ethanol (170 ml) with concentrated hydrochloric acid (2 ml) and p-toluene-
sulphonyl chloride (0.1 g) for 55 hours. The solvent was evaporated and ice water added to the residue, which was then neutralised with solid sodium bicarbonate. The mixture was extracted with chloroform, insoluble material filtered, the organic extract dried over magnesium sulphate and evaporated to give 3-aminopyridazine-4-carboxylic acid ethyl ester
15    (1.02 g) as a white solid.
NMR (CDC13) 8 ppm: 1.40 (t,3H), 4.40 (q,2H), 6.50 (bs,2H), 7.74 (d,1H), 8.72 (d,1H). Step 2
The product from Step 1 (0.36g) was dissolved in dry toluene (25 ml) and DMAP
(0.262 g) was added. A solution of 2,4,6-trifluorophenylacetyl chloride (0.45 g) in dry
20    toluene (1 nil) was added dropwise with stirring, and a white precipitate formed. After
stirring at room temperature for 10 minutes the reaction was stirred under reflux for 4.5 hours, and then allowed to stand overnight at room temperature. The white solid was filtered and washed with toluene, and the filtrate evaporated to give a brown oil, which was purified by HPLC eluting with ethyl acetate:hexane 4:1 to give 342-(2,4,6-trifluoropheny1)-
25        acetylamino]-pyridazine-4-carboxylic acid ethyl ester as a pale yellow solid (0.57 g), m.p.
135°C.
'H NMR (CDCI3) 8 ppm: 1.40 (t,3H), 4.22 (s,2H), 4.41 (q,2H), 6.70 (m,2H), 7.94 (d,1H), 9.15 (d,1H), 10.30 (bs,1H).
 
- 68 -
Step 3
The product from Step 2 (2.0 g) was dissolved in dry THF (50 ml), and sodium bis-trimethylsilylamide (17.7 ml of a 1.0M solution in THF) was added dropwise with stirring under nitrogen at 0°C. The reaction was stirred for 3 hours at 0°C and a yellow precipitate
5    was formed. The reaction was quenched with concentrated hydrochloric acid and then
poured into ice water. The solid was filtered, washed with water and air dried to give 6- (2,4,6-trifluoropheny1)-8H-pyrido[2,3-c]pyridazine-5,7-dione as a yellow solid (1.9 2g), m.p. >330°C, still containing some THF, which was used without further purification.
'H NMR (D6-DMSO) 8 ppm: 7.30 (m,2H), 8.10 (d,1H), 9.20 (d,1H), 11.90 (bs,1H), 12.60
10    (s,1H).
Step 4
The product from Step 3 (0.060 g) was heated to 90°C in phosphorus oxychloride (1
ml) for 1 hour to give a clear black solution. The mixture was cooled and the excess in phosphorus oxychloride evaporated. The residue was quenched with ice and aqueous sodium
15    bicarbonate, extracted with ethyl acetate, the extract dried over magnesium sulphate and
evaporated to give 5,7-dichloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-c]pyridazine as a black solid (0.087 g).
1H NMR (CDC13) 8 ppm: 6.90 (m,2H), 8.30 (d,1H), 9.75 (d,1H).
Step 4
20 The product from Step 3 (0.080 g) was stirred with isopropylamine (2 ml) in DCM (5 ml) at
room temperature overnight and then heated to 40°C in a sealed tube for 4 hours. The
volatiles were evaporated, water was added and the mixture extracted with DCM. The extracts were dried over magnesium sulphate and evaporated to give a dark brown tar, which was purified by preparative TLC on silica gel plates eluting with ethyl acetate:hexane 3:2 to
25    give
[7-Chloro-6-(2,4,6-trifluoropheny1)-pyrido[2,3-c]pyridazin-5-y1Fisopropylamine (0.008 g), 11-1 NMR (CDCI3) 8 ppm: 1.20 (d,6H), 3.71 (m,1H), 4.45 (bs,1H), 6.87-6.92 (m,2H), 7.97 (d,1H), 9.37 (d,1H).
30
 
- 69 -
Table 133
Comp ound No.    Table No.    Compound Structure    NMR data (ppm, in CDC13, unless otherwise stated) or Mpt.   
3    1    F        1.1 (d,6H), 3.26 (m,1H), 6.84 (m,2H), 6.95   
        40        (bd,IH), 8.67 (d,1H), 9.0 (d,1H).   
        CI F           
4    1            0.8 (t,3H), 1.27 (m,2H), 1.55 (m,2H), 2.87   
        N}:-.F        (m,2H), 6.8,6.85 (ABd,2H); 8.66, 8.99   
        01
■        (ABd,2H).   
        --.    N    CIF           
14    1    A
NH    F    129-131°C   
        si           
        F           
        N    CI           
15    1    F
NH    F    149-150°C   
                   
        F           
        CI           
16    1    F        175-177°C   
                   
        F
Ili    40)           
        F           
        CI           
17    1            153-155°C   
        NH    0111           
22    1    6        0.92 (m) + 1.22 (m) +1.55 (m) (total = 8H),    2.9
        N    40F
rL        (m,2H), 6.85 (m,2H), 8.78,8.96 (ABd,2H).   
        N    N    Ct           
23    1    NN        151-153°C   
        N    a           
 
- 70 -
58    1    NHF gam
,    "..    11111111
,    i    F
N    a    102-104°C
108    1    F
NH 0
I'L
F
ci    1.12 (d,3H), 3.27 (m,2H), 3.3 (s,3H), 3.5 (m,1H), 6.8 (m,2H), 8.67 (d) + 8.97 (ABd) (total = 21-1)
161    1    FSi
-CIF    138-140°C
162    1    0 F
N
 N    CI F    140-141°C
219    1    / F
----N    is
N    N CI F    3.0 (s,6H), 6.85 (m,21-1), 8.65,8.87 (ABd,2H)
3    5    ,J'• NHF 40
N
CI CI    157-159°C
4    5    miF 40
CN N    CI    0.82 (m,31-1),1.22 m + 1.5 m (total = 41-1), 2.82 (m,2H), 7.1-7.47 (m,3H), 8.67 + 9.05 (ABd ,2H).
17    5    F
NH 40
c,
N    Ct    159-160°C
20    5    -,..    ---..    11.
C
/    /    I
N    N    CI    166-168°C
 
- 71 -
22    5    F
NH 00
N    N /    /    a
Cl    163-165°C
23    5    F    163-165°C
        NH 0   
        /    CI   
        N    CI   
28    5    F    71-73°C
        N.   
        ...-    ,    CI   
        N    CI   
108    5        1.05 (d) + 1.12 (d) (total = 3H), 3.1-3.5 (m,3H),
        0    3.25 (d) + 3.32 (d) (total = 3H), 7.1 (m) + 7.4
        CNCI
CI    (m) (total = 4H), 8.67 (d,1H), 9.06 (d,1H)
161    5    F    0.82 (m,4H), 3.65 (m,4H), 7.12-7.35 (m,3H),
            8.66 + 8.87 (ABd,2H).
        1 CI   
162    5        1.52 (m,6H), 3.3 (m,4H), 7.25 (m) + 7.4 (m)
        ,, Si    (total = 3H), 8.78 + 8.95 (ABd,2H).
        ,    1 CI   
171    5        2.3 (s,3H), 2.5 (m,4H), 7.15 (m,1H), 7.37
        CND F 40    (m,2H), 8.75 (d,1H), 8.92 (d,1H).
        Cl   
3    11        1.16 (d,6H), 3.41 (m,1H), 6.85 (dd,2H), 7.79
        ---"-NH    Si
N,N    (bs,1H), 7.84 (d,1H). 9.40 (d,1H).
        /    F   
        N    CI   
 
-72-
23    11    FNH ,N
N    CI F    0.79 (t,3H), 1.11 (d,3H), 1.47 (m,2H), 3.13
(M, I H), 6.86 (dd,2H), 7.79 (bs,1H), 7.84 (d,1H), 9.40 (d,1H).
3    21        1.27 (d,6H), 4.05 (m,1H), 4.90 (bs,1H), 6.92
        „„....,NHF   
        0    (m,2H), 9.55 (s,1H), 9.90 (s,1H).
        N'-•    .N-
i I   
        N    F
,..'   
        CI   
3    26    F    1.20 (d,6H), 3.71 (m,1H), 4.45 (bs,1H), 6.87-
        --/-"NHF 0    6.92 (m,2H), 7.97 (d,1H), 9.37 (d,1H).
        I   
            NON    ..,    F
    N    N    CI   
3    31    NHF    iallt    1.25 (d,6H), 4.5 (bd,1H) 4.6 (m,1H), 7.15 (t,2H), 7.6 (m,1 H), 8.625 (fd,1H), 8.85 (fd,1H).
        CIF   
3    32        1.10 (d,6H), 4.52 (m,2H), 7.28 (m,3H), 7.47
        0    (m,1H), 8.52 (d,1H), 8.76 (d,1H)
        '''..,    -N2--
I    F   
        N    N    CI   
23    32        0.78 (m,3H), 1.07 (m,3H), 1.45 (m,2H), 4.48
        NH    411)    (m,21-1), 7.25 (m,3H), 7.50 (m,1H), 8.51 (d,1H),
            8.71 (d,1H)
        CI   
3    37    a    160-161 °C
        NH 0   
        N   
        CN    N    CI CI   
16    37        181-183°C
        a   
        Ni
0
a a   
171    37        2.3 (s,3H), 2.5 (m,3H), 3.2-3.5 (m,4H), 7.27 (m)
        0    + 7.4 (In) + 7.62 (m) (total = 3H), 8.77 (d,1H),
        a a    8.92 (d,1H).
 
-73-
3    43    HN    410
.--    --    Br
N    N    CI    HO (d,6H), 4.32 (d,IH), 4.57 (m,1H), 7.22 (M, IH), 7.35 (m,1H), 7.48 (m,1H), 7.78 (m,H), 8.53 (d, I H), 8.71 (d,1H)
23    43    NH Br 0
N    N    CI    0.81 (m,3H), 1.10 (m,3H), 1.40 (m,2H), 4.26 (m,1H), 4.45 (m,1H), 7.25 (m,1H), 7.38 (m,1H), 7.50 (m,1H), 7.76 (m,1H), 8.52 (d,1H), 8.74 (d,1H)
3    103    N
L    010    127-128°C
5    103    >IN,    F
NH 40
N
N    N    F F    138-140°C
12    103    FZ,F
NH 40
,    106-108 °C
14    103        6,    F
NH
    CN    40
N    FF    120-121°C
15    103    F
NH el
N --.    -N.
N    153-154°C
23    103    NH
,--    ,    FN    F    101-102°C
 
- 74 -
58    103    Y
N NH •
N
CN    / F F    99-100 °C
92    103    F 0
NH    1.07 (t,3H), 1.57 (s,3H), 3.52 (s,2H), 3.72 (q,2H), 4.85 (m,2H), 6.85 (m,211), 8.8 (d,1H), 9.0 (d,1H).
161    103    N
N    N    F    148-150°C
171    103    I
N
:    167-160°C
2651    103    F
NH
--N,    141111
'L.F CI    100-101 °C
2660    103    F3c),,,
H    NHF
N    --...
.--    CI
N    N    F    1.3 (d,3H), 1.4 (d,3H), 3.9 (m,1H), 6.95-7.6 (m,4H), 8.75 (m,1H), 9.05 (m,1H).
2671    103    NHF
IN
CI
F    123-124°C
2706    103    Y
NHF *
,    F CI    0.8 (m,6H), 1.72 (m,1H), 2.6 (m,2H), 7.02 - 7.47 (m,4H), 8.6 (d,1H), 8.92 (d,1H).
 
- 75 -
43704    103    F3c),,,    a
H    NH
CI
N    F    133-135 °C (diastereoisomer 1)
43704    103        F3C>L    CI
H
CN  NH .
...,
     N    F    CI    137-139 °C (diastereoisomer 2)
43715    103    CI
NH 0
1    '....,    '-----    CI
N    F    118-119 °C
43750    103    CI
NH    40,
....-    ,    F    CI    0.80 (d) + 0.83 (d) (total = 6H), 1.72 (m,1H), 2.65 (m,2H), 7.1-7.3 (m) + 7.35,7.6 (d) (total = 3H), 8.6 (d,1H), 8.92 (d,1H).
1    128    COOMe
N    NHF 40 F
O    4.03 (s,5H), 6.74 (t,2H), 8.43 (d,1H), 8.61 (d,1H) 10.9 (s,1H).
6    128    C    oN    C OMe
N%\NHF
O
CI    162-163°C
12    128    N COOMe
CN~NH    CI
411
O
ci    158-159°C
13    128    N,N    COOMe
7 NHF eiF    1.48 (t,3H), 4.52 (q,2H), 6.73 (d,1H), 8.75 (d,1 H).
 
-76-
25    128    N--`.-    COOMe
II
N / NHF 5F
O
F    1.45 (t,3H), 3.90 (s,2H), (4.45 (q,2H), 6.75 (m,2H), 9.45 (s1H), 10.60 (s, I H), 11.1 (bs,1H).
37    128    COOMe    1.40 (t,3H), 4.22 (s,2H), 4.41 (q,2H), 6.70
        N,
NHF 0F
O    (m,2H), 7.94 (d,1H), 9.15 (d,1H), 10.30 (bs,1H).
        F   
1    129    F    F    (d6-DMSO) 7.25(1,211), 8.6(fd,1H),8.7(fd,1H),
        OH    012.6(s,1H).   
        N .---    ---
 N    OHF   
6    129    OHF 40    >220°C
        N   
        OHI
N N    C   
9    129    OH    250-252 °C
        N    0   
        N    OHF   
11    129    OH    258 °C
        N    5   
        N    N    OHBr   
12    129    •    0 CI    >200 °C
        CN   
        N    N    OHCI   
13    129    O F    (CD3OD) 6.83 (2d,2H), 7.44 (d,1H), 9.00
        N.    5    (d,1H).
        ./
N   
        H   
25    129    O F    F    (d6-DMS0) 7.25 (m,2H), 9.17 (s,1H), 9.47
        I. N
II    (S, 1H), 12.30 (bs,IH).
        N    ,---   
        N   
        H   
 
-77-
37    129    N    i
N    0 F0
I
F
N    0
H        (D6-DMS0) 7.30 (m,2H), 8.10 (d,1H), 9.20 (d,1H), 11.90 (bs,1H), 12.60 (s,1H).
1    130    ,
...,    ---
N    F    F
0 0
---
N    CI F        139-141°C
6    130    i Nf'    CIF 0
.,    c,
CI        154-155 °C
9    130    .-N
,,N    CI 0
F
CI        7.21(m,1H), 7.28(m,2H), 7.48(m,1H), 8.95(d,1H), 9.08(d,1 H).
11    130    N
..---    ,...,
,_N---    CI 0
CI Br        7.18(d, 111), 7.29(m,1H), 7.41(t,1H), 7.69(dd,1H), 9.00(d,1H), 9.09(d,1H).
12    130    CN    ci    0 GI
N.'    CI CI    F    159-160°C
13    130    ,N
N    CI F
CI F        6.92 (m,2H), 8.11 (d, IH), 9.71 (d,1H).
25    130    N
II
N    ,,/    CIF Si
F
CI        6.90 (m,2H), 9.80 (s,1H), 10.0 (s, H).
37    130    N
N    CIF I.
F
N    CI        6.90 (m,2H), 8.30 (d,1H), 9.75 (d,1H).
 
-78-
I    131    N    F
/
N    .
F
F        120-121°C
6    131        F F            7.27 (m) + 7.55 (m) (total = 31-1), 9.07 (d, I H),
        ,IV    ---.            9.2 (d,1H).
        -..
N        CI
F       
12    131        F        a    7.45 (m) + 7.67 (d) (total =- 311), 9.07 (d,1H), 9.2
            ---.            (d,1H).
        N    N    F CI       
                       

EXAMPLE 6
This Example illustrates the fungicidal properties of the compounds of the general 5    formula (1).
Compounds were tested in a leaf disk assay, with methods described below. Test compounds were dissolved in DMSO, and diluted into water to 200 ppm.
Plasmopara viticola (downy mildew of grapevine): grapevine leaf disks were placed on agar in a 24-well plate and sprayed a solution of the test compound. After allowing to dry
10 completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed seven days after inoculation as preventive fungicidal activity.
Phytophthora infestans (late blight of potato on tomato): tomato leaf disks were placed on water agar in a 24-well plate and sprayed with a solution of the test compound. After
15    allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with
a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
Erysiphe graminis f sp. hordei (barley powdery mildew): barley leaf segments were placed
on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing
20    to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore
suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
Erysiphe graminis fsp. tritici (wheat powdery mildew): wheat leaf segments were placed
 
-79-
on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore
suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
5    Puccinia recondita fsp. tritici (wheat brown rust): wheat leaf segments were placed on agar
in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore
suspension of the fungus. After appropriate incubation the activity of a compound was assessed nine days after inoculation as preventive fungicidal activity.
10 Septoria nodorum (wheat glume blotch): wheat leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore
suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
15 Pyrenophora teres (barley net blotch): barley leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore
suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
20    Pyricularia oryzae (rice blast): rice leaf segments were placed on agar in a 24-well plate and
sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
25    Botrytis cinerea (grey mould): bean leaf disks were placed on agar in a 24-well plate and
sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.
30 The following compounds gave greater than 60% control of disease:
Plasniopara viticola, Compounds 4 (1), 20 (1), 23 (5);
Phytophthora infestans, Compounds 3 (1), 58 (5), 3 (103);
 
- 80-•
Erysiphe graminis fsp. hordei, Compounds 3 (1), 14 (1), 15 (1), 16 (1), 17 (1), 22 (1), 23 (1), 58 (1), 108 (1), 161 (1), 162 (1), 3 (5), 4 (5), 17 (5), 20 (5), 22 (5), 23 (5), 28 (5), 58 (5), 108 (5), 162 (5), 171 (5), 665 (31), 23 (32), 3 (37), 16 (37), 171 (37), 665 (37), 678 (37), 3 (43), 23 (43), 685 (43), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103), 2660 (103),
    5    2671 (103), 23844 (103) diastereoisomer 1, 23844 (103) diastereoisomer 2, 23855 (103),
23890 (103;
Erysiphe graminis fsp.tritici, Compounds 3 (1), 4 (1), 15 (1), 16 (1), 22 91), 23 (1), 58 (1),
108 (1), 162 (1), 219 (1), 58 95), 161 (5), 3 (31), 16 (37), 665 (37), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer
    10    1, 23844 (103) diastereoisomer 2, 23855 (103), 23890 (103);
Puccinia recondita fsp. tritici, Compounds 3 (1), 14 (1), 15 (1), 16 (1), 17 (1), 23 (1), 58 (1),
108 (1), 161 (1), 162 (1), 4 (5), 17 (5), 23 (5), 28 (5), 58 (5), 108.(5), 3 (31), 16 (37), 665
(37), 678 (37), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23855 (103), 23890 (103);
    15    Septoria nodorum, Compounds 3 91), 15 (1), 16 (1), 17 (1), 23 (1), 58 (1), 58 95), 161 (5),
22 (6), 665 (37), 685 (43), 12 (103), 23 (103), 58 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23855 (103), 23890 (103);
Pyrenophora teres, Compounds 3 (1), 14 (1), 15 (1), 16 (1), 17 (1), 23 (1), 58 (1), 161 (1), 3
(5), 20 (5), 16 (37), 665 (37), 3 (103), 12 (103), 23 (103), 58 (103), 2651 (103), 2660 (103),
    20    2671 (103), 23844 (103) diastereoisomer 1, 23855 (103), 23890 (103);
Pyricularia oryzae, Compounds 3 (1), 4 (1), 14 (1), 15 (1), 16 (1), 17 (1), 20 (1), 23 (1), 58 (1), 108 (1), 161 (1), 3 (5), 4 (5), 20 (5), 23 (5), 58 (5), 108 (5), 3 (32), 3 (37), 16 (37), 678 (37), 3 (43), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 171 (103), 2651 (103), 2669 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23844 (103) diastereoisomer 2, 23855
    25    (103), 23890 (103);
Botrytis cinerea, Compounds 4 (1), 14 (1), 15 (1), 16 (1), 17 (1), 22 (1), 58 (1), 108 (1), 4
(5), 22 (5), 28 (5), 58 (5), 108 (5), 162 (5), 16 (37), 678 (37), 23 (103), 92 (103), 2651 (103), 2660 (103), 23844 (103) diastereoisomer 2, 23855 (103), 23890 (103).
 
- 81 -
CLAIMS
1.    The compound of the general formula (1):
R2
 

 
5 wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C18 alkyl, C1_4 alkoxy or halo(C1-0)alkyl;
R is halo;
R' is halo, C1_8 alkyl, C2_8 alkenyl, C2_8 alkynyl, C3_8 cycloalkyl, C3.8 cycloalkyl(C1_6)alkyl,
10    C1.8 alkoxy, C1_8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio,
aryl(C1.4)alkyl, aryl(C1_4)alkoxy, heteroaryl(C1_4)alkyl, heteroaryl(Ci4alkoxy, aryl(C14)alkylthio, heteroaryl(C14alkylthio, morpholino, piperidino or pyrrolidino;
R2 is NR3R4;
R3 and R4 are independently H, C1_8 alkyl, C2.8 alkenyl, C2_8 alkynyl, aryl, aryl(C1_8)alkyl,
15        C3-8 cycloalkyl, C3-8 cycloalkyl(C1.6)alkyl, heteroaryl, heteroaryl(C1.8)alkyl, NR5R6, provided
that not both R3 and R4 are H or NR5R6, or
R3 and R4 together form a C3_7 alkylene or C3_7 alkenylene chain optionally substituted with one or more C1_4 alkyl or C,4 alkoxy groups, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine,
20 thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N-(C1.4)alkyl (especially N-methyl) ring; and
R5 and R6 are independently H, C1_8 alkyl, Cm alkenyl, C2_8 alkynyl, aryl, aryl(C1_8)alkyl, C3_8 cycloalkyl, C3_8 cycloalkyl(C1_6)alkyl, heteroaryl or heteroaryl(C1_8)alkyl;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
25    R8) being optionally substituted with halogen, cyano, C1_6 alkoxy, C, 6 alkylcarbonyl,
CI _6 alkoxycarbonyl, C1_6 haloalkoxy, C1_6 alkylthio,    C1_6 alkylamino or
C1_6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C,4 alkyl (especially methyl), and
 
- 82 -
any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C1-6 alkyl, C2.6 alkenyl,
C2.6 alkynyl, C1.6 alkoxy, C2_6 alkenyloxy, C2_6 alkynyloxy, halo(C1_6)alkyl, halo(C1_6)alkoxy, C1.6 alkylthio, halo(C1.6)alkylthio, hydroxy(C1_6)alkyl, CIA alkoxy(Ci_6)alkyl, C3_6 cycloalkyl,
5        C3_6 cycloalkyl(C14)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato,
isothiocyanato, nitro, -NR"'R"", -NHCOR"', -NHCONR'"R"", -CONR'"R"",
-0S02R'", -COR'", -CR'"=NR"" or -N=CR"R"", in which R"' and R"" are independently hydrogen, C1.4 alkyl, halo(C14)alkyl, CIA alkoxy, halo(C14alkoxy, C14 alkylthio,
C3.6 cycloalkyl, C3-6 cycloalkyl(Cm)alkyl, phenyl or benzyl, the phenyl and benzyl groups
10    being optionally substituted with halogen, C14 alkyl or C14 alkoxy.
2.    A compound according to claim 1 wherein W and Z are N and X and Y are CH.
3.    A compound according to any one of the preceding claims wherein
15    R3 is C1_8 alkyl, halo(C1_8)alkyl, hydroxy(C1_8)alkyl, C1-4 allWXy(Ci_8)alkyl, C1.4 alkoxyhalo-
(Ci_8)alkyl, tri(C1.4)alkylsilyl(C1_6)alkyl,    alkylcarbonyl(Ci_8)alkyl, C14 alkylcarbonyl-
halo(C1.8)alkyl, phenyl(14)alkyl, C2.8 alkenyl, halo(C2.8)alkenyl, C2.8 alkynyl, C3.8 cycloalkyl optionally substituted with chloro, fluoro or methyl, C3.8 cycloalkyl(CIA)alkyl, phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally
20        substituted with one, two or three substituents selected from halo, C14 alkyl, halo(C14alkyl,
C1.4 alkoxy and halo(CiA)alkoxy; and
R4 is H, C1.4 alkyl, halo(C14)alkyl or amino, or
R3 and R4 together form a C3.7 alkylene or alkenylene chain optionally substituted with methyl, or,
25    together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine,
thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N-(C1_4)alkyl (especially N-methyl) ring, in which the morpholine or piperazine rings are optionally substituted with methyl.
30 4.    A compound according to any one of the preceding claims wherein
R1 is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C1_4 alkyl, halo(C14)alkyl, Ci4 alkoxy or halo(CIA)alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with
 
- 83 -
from one to three substituents selected from halo, Ci4 alkyl, halo(C14)alkyl, C14 alkoxy or halo(C1..4)alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C14 alkyl, halo(CIA)alkyl,
CI alkoxy or halo(Ci,t)alkoxy, or piperidino or morpholino both optionally substituted with
5    one or two methyl groups.
5.    A compound according to claim 4 wherein R' is 2,6-difluorophenyl, 2-fluoro-6-
chlorophenyl, 2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl, 2,6-difluoro-4-methoxyphenyl or pentafluorophenyl.
10
6.    A compound according to claim 1 wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C1-4 alkyl, C14 alkoxy or halo(C1_4)alkyl;
R is halo;
15    R' is halo, Ci_s alkyl, C2-8 alkenyl, C2_8 alkynyl, C3.8 cycloalkyl, C3.8 cycloalkyl(C1_6)alkyl,
C1.8 alkoxy, C1.8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(Ci4)alkyl, aryl(C14)alkoxy, heteroaryl(C14)alkyl, heteroaryl(C14alkoxy, aryl(C1-4)- allcylthio, heteroaryl(C14alkylthio, morpholino, piperidino or pyrrolidino;
R2 is NR3R4 ;
20    R3 and R4 are independently H, C1.8 alkyl, C2-8 alkenyl, C24 alkynyl, aryl, aryl(C1_8)alkyl,
C3.4 cycloalkyl, Cg_g cycloalkyl(C1_6)alkyl, heteroaryl, heteroaryl(C1.8)alkyl, NR5R6, provided that not both R3 and R4 are H or NR5R6, or
R3 and R4 together form a C3_7 alkylene or C3_7 alkenylene chain optionally substituted with one or more C14 alkyl or C1.4 alkoxy groups, or,
25    together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine,
thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N-(C1_4)alkyl (especially N-methyl) ring; and
R5 and R6 are independently H, C1 alkyl, C2-g alkenyl, C2.8 alkynyl, aryl, aryl(C1_8)alkyl, C3_8 cycloalkyl, C3_8 cycloalkyl(Ci_6)alkyl, heteroaryl or heteroaryl(C1_8)alkyl;
30    any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
R8) being optionally substituted with halogen, cyano, C1_6 alkoxy, C1.6 alkylcarbonyl, C1_6alkxycarbonyl, C1.6 haloalkoxy, C1.6 alkylthio, tri(C1.4)alkylsilyl, C1.6 alkylamino or C1_6 dialkylamino,
 
-84-
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C14 alkyl (especially methyl), and
any of the aryl, heteroaryl, aryloxy or heteroaryl groups being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C1_6 alkyl, C2-6 alkenyl,
    5    C2_6 alkynyl, C1_6 alkoxy, C2_6 alkenyloxy, C2-6 alkynyloxy, halo(C1_6)alkyl, halo(C14)alkoxy,
C1_6 alkylthio, halo(C1-6) alkylthio, hydroxy(C1_6)alkyl, C14 alkoxy(C1_6)alkyl, C3_6 cycloalkyl, C3_6 cycloalkyl(C1_4)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, -NR"'R'"', -NHCOR'", -NHCONR"'R'', -CONR"'R"",
-0S021r, -COR"', -CR"'=NR"" or -N=CR'"R"", in which R"' and R"" are independently
    10    hydrogen, C14 alkyl, halo(C14alkyl, C14 alkoxy, halo(C14)alkoxy, C14 alkylthio,
C3.6 cycloalkyl, C3_6 cycloalkyl(Ci4allcyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C14 alkyl or C14 alkoxy.
7.    A compound according to claim 1 wherein
15 W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(C1_4)alkyl;
R is halo;
RI is halo, Ci_s alkyl, C2-8 alkenyl, C2-8 alkynyl, C3_8 cycloalkyl, C3_8cycloalkyl(C14)alkyl, C1_8 alkoxy, C1-8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio,
    20    aryl(C1.4)alkyl, aryl(C1.4)alkoxy, heteroaryl(C1.4)alkyl, heteroaryl(C14alkoxy,
aryl(C14)alkylthio, heteroaryl(C1_4)alkylthio, morpholino, piperidino or pyrrolidino;
R2 is NR3R4;
R3 is C14 alkyl, halo(C1_4)alkyl, C2.4 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1_4)alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three subs-
    25    tituents selected from halo, C14 alkyl, halo(Ci_4)alkyl, C14 alkoxy and halo(C14alkoxy; and
R4 is H, C14 alkyl or amino, or
R3 and R4 together form a C4.6 alkylene chain optionally substituted with C14 alkyl or C14 alkoxy, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine,
    30    thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazine N-(CI4alkyl (especially N-methyl) ring;
any of the alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R8) being optionally substituted with halogen, cyano, C1_6 alkoxy, C1_6alkylcarbonyl,
 
- 85 -
C14, alkoxycarbonyl, C1_6 haloalkoxy, C1_6 alkylthio, tri(C14)alkylsilyl, C1_6 alkylarnino or C1_6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C14 alkyl (especially methyl), and
5    any of the aryl or heteroaryl groups or moieties being optionally substituted with one or more
substituents selected from halo, hydroxy, mercapto, C1_6 alkyl, C2_6 alkenyl, C2-6 alkynyl, Ci_6 alkoxy, C2-6 alkenyloxy, C2_6 alkynyloxy, halo(C1_6)alkyl, halo(C1_6)allcoxy,
C1_6 alkylthio, halo(C14)alkylthio, hydroxy(C1_6)alkyl, C14 alkoxy(C1_6)alkyl, C3_6 cycloalkyl, C3_6 cycloalkyl(C14alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato,
10    isothiocyanato, nitro, -NR"'R'"', -NHCOR"', -NHCONRs"R"", -CONR"'R"", -S021r,
-0S021r, -COR"', -CR"'=NR"" or -N=CR"'R"", in which Rs" and R"" are independently hydrogen, C14 alkyl, halo(Ci4alkyl, C14 alkoxy, halo(C14alkoxy, CI4 alkylthio,
C3_6 cycloalkyl, C3_6 cycloalkyl(C1_4)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, Ci4 alkyl or C14 alkoxy.
15
8.    A compound according to claim 1 wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(Cj4alkyl;
R is halo;
20    R' is optionally substituted phenyl;
R2 is NR3R4;
R3 and R4 are independently H, Cl_s alkyl, C2_8 alkenyl, C2-8 alkynyl, aryl, aryl(C1_8)alkyl, C3_8 cycloalkyl, C3_8cycloalkyl(C1_6)alkyl, heteroaryl, heteroaryl(C1_8)alkyl, NR5R6, provided that not both R3 and R4 are H or NR5R6, or
25    R3 and R4 together form a C3_7 alkylene or C3_7 alkenylene chain optionally substituted with
one or more C14 alkyl or C14 alkoxy groups, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N-(C14)alkyl (especially N-methyl) ring; and
30    R5 and R6 are independently H, Ci_g alkyl, C2_8 alkenyl, C2-8 alkynyl, aryl, aryl(C1_8)alkyl,
C3_8 cycloalkyl, C3_8cycloalkyl(C1.6)alkyl, heteroaryl or heteroaryl(Ci_8)alkyl;
any of the alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R8) being optionally substituted with halogen, cyano, C1_6 alkoxy, CI-6 alkylcarbonyl, CI-6
 
- 86 -
alkoxycarbonyl, C1-6 haloalkoxy, C14, alkylthio, tri(C14)alkylsilyl, Ci.6 alkylamino or Ci_o dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C14 alkyl (especially methyl), and
5    any of the aryl or heteroaryl groups or moieties, including the phenyl group of R1, being
optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C1_6 alkyl, C2-6 alkenyl, C2_6 alkynyl, C1.6 alkoxy, C2_6 alkenyloxy, C2_6 alkynyloxy, halo(C1_6)alkyl, halo(C1_6)alkoxy, C1_6 alkylthio, halo(C1_6)alkylthio, hydroxy(C1_6)alkyl,
C14 alkoxy(Ci4)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C14)alkyl, phenoxy, benzyloxy,
10    benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, -NR'"R"", -NHCORm,
-NHCONR'"R"", -CONR"'Rm,    -OSO2R1", -CORM, -CR"'=NR'"' or -N=CR"'R"", in
which R"' and R"" are independently hydrogen, C14 alkyl, halo(C14)alkyl, C14 alkoxy, halo(Ci4)alkoxy, C14 alkylthio, C3_6 cycloalkyl, C3_6 cycloalkyl(C14)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C14 alkyl or
15    C14 alkoxy.
9.    A compound according to claim 1 wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(C14)alkyl;
20    R is halo;
RI is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C14 alkyl, halo(C14)alkyl, C14 alkoxy or halo(C14)alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo, C14 alkyl, halo(C14)alkyl, C14 alkoxy or
25        halo(C1.4)alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms
or with from one to three substituents selected from halo, C14 alkyl, halo(C1_4)alkyl,
C14 alkoxy or halo(C14)alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups;
R2 is NR3R4;
30    R3 is C1_8 alkyl, halo(C1_8)alkyl, hydroxy(C1_8)alkyl, C14 alkoxy(C _8)alky 1, C14 alkoxyhalo-
(C1_8)alkyl, tri(C14)alkylsilyl(C1_6)alkyl, C14 alkylcarbonyl(C1_8)alkyl, C14 alkylcarbonyl-halo(C1_8)alkyl, phenyl(14)alkyl, C2.8 alkenyl, halo(C2_8)alkenyl, C2.8 alkynyl, C3_8 cycloalkyl optionally substituted with chloro, fluoro or methyl, C:38 cycloalkyl(C14alkyl, phenylamino,
 
- 87 -
piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C14 alkyl, halo(C1.4)alkyl, Ci_4 alkoxy and halo(Ci4)alkoxy; and
R4 is H, C14 alkyl, halo(C1.4)alkyl or amino, or
5    R3 and R4 together form a C3_7 alkylene or C327 alkenylene chain optionally substituted with
methyl, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N-(C1_4)alkyl (especially N-methyl) ring, in which the morpholine or piperazine
10    rings are optionally substituted with methyl.
10.    A compound according to claim 1 wherein
W and X, W and Z, X and Y or Y and Z are N and the other two are CR8;
R8 is H, halo, C14 alkyl, C14 alkoxy or halo(C14)alkyl;
15    R is halo;
RI is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C14 alkyl, halo(C1.4)alkyl, C14 alkoxy or halo(C14)alkoxy;
R2 is NR3R4;
20    R3 is C14 alkyl, halo(C14)alkyl, C24 alkenyl, C3_6 cycloalkyl, C3_6 cycloalkyl(C14alkyl or
phenylamino in which the phenyl ring is optionally substituted with one, two or three substituents selected from halo, C14 alkyl, halo(C1.4)alkyl, C14 alkoxy and halo(C14)alkoxy; and
R4 is H, C14 alkyl or amino, or R3 and R4 together form a C4.6 alkylene chain optionally 25    substituted with methyl, or, together with the nitrogen atom to which they are attached, R3
and R4 form a morpholine ring.
1 1.    A process for preparing a compound of the general formula (1) according to claim 1
wherein R is chloro or fluoro and R2 is NR3R4 and W, X, Y, Z, RI, R3 and R4 are as defined 30    in claim 1, which comprises reacting an amine of the general formula NR3R4 with a
compound of the general formula (6) or (13)
 
CI
II    ii
Y,    Y..    .,-.A--    .---'
"z    N    a    'z    NI    F
03)    113
12,    The ratermediate ch.crnicars Wilting the genera formulae (4)-, (5), (6) and (13):
0
 

 
5    wherein W,    Y, Z anal RI are as definc4 .TI ul.raim 1 mid R7 i5 CI 4 alkyl, ocher than Lla:
corupOtinci .of formuLit (6) wlierEin X and Y r N, W    Z aft C-C] and R' is CL
13,    r1 plarti forogicida)cornprnitiort COMpFiSiTlg fuiligieldally effective arnoonc of a
compound    dernted in claim I Lind 0. stilttb1Q. carrii±1 or diluent llicrufor.
It    A method of coeraming or controlling ph vlopathogenic fungi which comprises
applying re a plank to a seed cra plaid, 10 the locus (If th4 plant or seed or    41/- any
olhcr plant growth =ilium, a ftingi.citially effective amourn of a compound according l claim I. or a fornrivlition ktccording to claim 13.
15
indexation.Ist QCOK tags.Ist

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