GB2307177A - Fungicidal pyridopyrimidines - Google Patents

Abstract

Substituted pyrido[1,2-a]primidinones of formula I wherein R 1 is an optionally substituted aryl or heteroaryl group; Z is O or S; W is O, S(O) n or NR 3 ; R 2 and R 3 , which may be the same or different, are each hydrogen or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group; each X, which may be the same as or different from any other X, is halogen, CN, NO 2 , SF 5 , acyl, O-acyl, trialkylsilyl, B(OH) 2 or a group D, OD or S(O) n D where D is a group as defined hereinbefore for R 2 or is optionally substituted amino and n is O, 1 or 2; or two adjacent groups X together with the atoms to which they are attached form a carbocyclic or heterocyclic ring; p is 0 to 4; and n is 0 to 2, most of which are novel compounds, have useful fungicidal activity.

Description

Fungicides This invention concerns compounds having fungicidal activity.

In one aspect, the invention provides the use in combating fungi of the substituted pyrido[1,2-a]pyrimidinones of the formula I

wherein R is an optionally substituted aryl or heteroaryl group; Z is O or S; W is O, S(O)n or NR3; R2 and R3, which may be the same or different, are each hydrogen or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group; each X, which may be the same as or different from any other X, is halogen, CN, NO2, SF5, acyl, O-acyl, trialkylsilyl, B(OH)2 or a group D, OD or S(O)nD where D is a group as defined hereinbefore for R2 or is optionally substituted amino and n is O, 1 or 2; or two adjacent groups X together with the atoms to which they are attached form a carbocyclic or heterocyclic ring; p is O to 4; and n is O to 2.

It will be appreciated that when R2 is hydrogen, the compounds of formula I can exist in the zwitterionic tautomeric form of formula la

Most of the above compounds are new, and we accordingly provide per se the compounds of formula I with the exception of the following compounds where Z is 0: B1 4?LBZ Ph OH 6-NH2 Ph OH 6-Me Ph OH 8-Me Ph OH Ph OH 9-OH Ph Oallyl Ph OCH2CH2NEt2- 4-OMePh OCH2CH2NEt 4-OMePh OH Any alkyl group present in the molecule is preferably of 1 to 10 carbon atoms, especially of 1 to 7 carbon atoms, and particuiarly of 1 to 5 carbon atoms, and may be unsubstituted or substituted.

Any alkenyl or alkynyl group present in the molecule is preferably of 2 to 7 carbon atoms, for example allyl, vinyl or propargyl.

Any cycloalkyl group present in the molecule is preferably of 3 to 7 carbon atoms, especially cyclopropyl, cyclopentyl, or cyclohexyl.

Substituents, when present on any alkyl, alkenyl, alkynyl or cycloalkyl moiety may for example be halogen, cyano, optionally substituted alkoxy, optionally substituted alkylthio, hydroxy, nitro, optionally substituted amino, acyl, acyloxy, optionally substituted phenyl, optionally substituted heterocyclyl, optionally substituted phenylthio, optionally substituted phenoxy, optionally substituted heterocyclyloxy, optionally substituted heterocyclylthio or oxidised derivatives of thio-containing groups.

Cycloalkyl groups may also be substituted by alkyl.

The term 'aryl' is used herein to mean aromatic carbocycles, which may be mononuclear, e.g. phenyl, or polynuclear, e.g. naphthyl. Any aryl group present in the molecule is preferably a substituted or unsubstituted phenyl group.

The term heteroaryl is used herein to mean aromatic heterocyclyl groups.

Heteroaryl groups are generally 5 or 6-membered rings containing up to 4 hetero atoms selected from nitrogen, oxygen and sulfur, optionally fused to a benzene ring. Examples of heteroaryl groups are those derived from thiophene, furan, pyrrole, thiazole, oxazole, imidazole, isothiazole, isoxazole, pyrazole, 1,3,4oxadiazole, 1,3,4-thiadiazole, 1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,2,4-triazole, 1,2,3-triazole, tetrazole, benzo[b]thiophene, benzo[b]furan, indole, benzo[c]thiophene, benzo[cjfuran, isoindole, benzoxazole, benzothiazole, benzimidiazole, benzisoxazole, benzisothiazole, indazole, benzothiadiazole, benzotriazole, dibenzofuran, dibenzothiophene, carbazole, pyridine, pyrazine, pyrimidine, pyridazine, 1,3,5-triazine, 1,2,4-triazine, 1,2,4,5-tetrazine, quinoline, isoquinoline, quinoxaline, quinazoline, cinnoline, 1 ,8-naphthyridine, 1,5naphthyridine, 1,6-naphthyridine, 1,7-naphthyridine, phthalazine, pyridopyrimidine, purine or pteridine.

The term heterocyclyl includes both heteroaryl groups as described above and nonaromatic heterocyclyl groups.

Non-aromatic heterocyclyl groups are generally 3, 5 or 6-membered rings containing up to 3 hetero atoms from nitrogen, oxygen and sulfur, for example oxiranyl, thiiranyl, thiazolinyl, dioxolanyl, 1,3-benzoxazinyl, 1,3-benzothiazinyl, morpholino, pyrazolinyl, sulfolanyl, dihydroquinazolinyl, piperidinyl, phthalimido, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, indolinyl, 2-oxopyrrolidino, 2 oxobenzoxazolin-3-yl.

Substituents when present on any aryl or heterocyclyl group may for example be halogen, CN, NO2, SF5, acyl, O-acyl or a group D, OD or S(O)nD as defined hereinbefore; or two adjacent groups on the ring together with the atoms to which they are attached form a carbocyclic or heterocyclic ring, which may be similarly substituted.

The term acyl includes the residue of sulfur and phosphorus-containing acids as well as carboxylic acids. Examples of acyl groups are thus -COR5, -COOR5, -CZNR5R6, -CON(R5)OR , -COONR 5R6, -CON(R5)NR 6R7, -COSR5, -CSSR5, S(O)qR5 -S(0)20R5, -S(o)qNR5R6, -P(=Z)(OR5)(OR6), -CO-COOR5, where R5, R6 and R7 which may be the same or different, are hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted phenyl or optionally substituted heterocyclyl, or R5 and R6, or R6 and R7, together with the atom(s) to which they are attached can form a ring, q is 1 or 2 and Z is O or S.

Amino groups may be substituted for example by one or two optionally substituted alkyl or acyl groups, or two substituents can form a ring, preferably a 5 to 7membered ring, which may be substituted and may contain other hetero atoms, for example morpholine.

The invention includes any compound of formula I and specifically exemplified.

The compounds of the invention have activity as fungicides, especially against fungal diseases of plants, e.g. mildews and particularly cereal powdery mildew (Erysiphe graminis) and vine downy mildew (Plasmopara viticola), rice blast (Pyricularia oryzae), cereal eyespot (Pseudocercosporefla herpotrichoides), rice sheath blight (Pellicularia sasakill, grey mould (Botrytis cinerea), damping off (Rhizoctonia soiani), wheat brown rust (Puccinia recondita), late tomato or potato blight (Phytophthora in fes tans), apple scab (Venturia inaequalis), glume blotch (Leptosphaeria nodorum). Other fungi against which the compounds may be active include other powdery mildews, other rusts, and general pathogens of Deuteromycete, Ascomycete, Phycomycete and Basidomycete origin.

The invention thus also provides a method of combating fungi at a locus infested or liable to be infested therewith, which comprises applying to the locus a compound of formula I.

The invention also provides an agricultural composition comprising a compound of formula I in admixture with an agriculturally acceptable diluent or carrier.

The composition of the invention may of course include more than one compound of the invention.

In addition the composition can comprise one or more additional active ingredients, for example compounds known to possess plant-growth regulant, herbicidal, fungicidal, insecticidal or acaricidal properties. Alternatively the compound of the invention can be used in sequence with the other active ingredient.

The diluent or carrier in the composition of the invention can be a solid or a liquid optionally in association with a surface-active agent, for example a dispersing agent, emulsifying agent or wetting agent. Suitable surface-active agents include anionic compounds such as a carboxylate, for example a metal carboxylate of a long chain fatty acid; an N-acylsarcosinate; mono- or di-esters of phosphoric acid with fatty alcohol ethoxylates or salts of such esters; fatty alcohol sulfates such as sodium dodecyl sulfate, sodium octadecyl sulfate or sodium cetyl sulfate; ethoxylated fatty alcohol sulfates; ethoxylated alkylphenol sulfates; lignin sulfonates; petroleum sulfonates; alkyl-aryl sulfonates such as alkyl-benzene sulfonates or lower alkylnaphthalene sulfonates, e.g. butyl-naphthalene sulfonate; salts of sulfonated naphthalene-formaldehyde condensates; salts of sulfonated phenol-formaldehyde condensates; or more complex sulfonates such as the amide sulfonates, e.g. the sulfonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulfosuccinates, e.g. the sodium sulfonate of dioctyl succinate. Nonionic agents include condensation products of fatty acid esters, fatty alcohols, fatty acid am ides or fatty-alkyl- or alkenyl-substituted phenols with ethylene oxide, fatty esters of polyhydric alcohol ethers, e.g. sorbitan fatty acid esters, condensation products of such esters with ethylene oxide, e.g.

polyoxyethylene sorbitan fatty acid esters, block copolymers of ethylene oxide and propylene oxide, acetylenic glycols such as 2,4,7,9-tetramethyl-5-decyne-4,7-diol, or ethoxylated acetylenic glycols.

Examples of a cationic surface-active agent include, for instance, an aliphatic mono-, di-, or polyamine as an acetate, naphthenate or oleate; an oxygen-containing amine such as an amine oxide or polyoxyethylene alkylamine; an amide-linked amine prepared by the condensation of a carboxylic acid with a dior polyamine; or a quaternary ammonium salt.

The compositions of the invention can take any form known in the art for the formulation of agrochemicals, for example, a solution, a dispersion, an aqueous emulsion, a dusting powder, a seed dressing, a fumigant, a smoke, a dispersible powder, an emulsifiable concentrate or granules. Moreover it can be in a suitable form for direct application or as a concentrate or primary composition which requires dilution with a suitable quantity of water or other diluent before application.

An emulsifiable concentrate comprises a compound of the invention dissolved in a water-immiscible solvent which is formed into an emulsion with water in the presence of an emulsifying agent.

A dusting powder comprises a compound of the invention intimately mixed and ground with a solid pulverulent diluent, for example, kaolin.

A granular solid comprises a compound of the invention associated with similar diluents to those which may be employed in dusting powders, but the mixture is granulated by known methods. Alternatively it comprises the active ingredient absorbed or adsorbed on a pre-granular diluent, for example, Fuller's earth, attapulgite or limestone grit.

Wettable powders, granules or grains usually comprise the active ingredient in admixture with a suitable surfactant and an inert powder diluent such as china clay.

Another suitable concentrate is a flowable suspension concentrate which is formed by grinding the compound with water or other liquid, a wetting agent and a suspending agent.

The concentration of the active ingredient in the composition of the present invention, as applied to plants is preferably within the range of 0.0001 to 1.0 per cent by weight, especially 0.0001 to 0.01 per cent by weight. In a primary composition, the amount of active ingredient can vary widely and can be, for example, from 5 to 95 per cent by weight of the composition.

In the method of the invention the compound is generally applied to seeds, plants or their habitat. Thus, the compound can be applied directly to the soil before, at or after drilling so that the presence of active compound in the soil can control the growth of fungi which may attack seeds. When the soil is treated directly the active compound can be applied in any manner which allows it to be intimately mixed with the soil such as by spraying, by broadcasting a solid form of granules, or by applying the active ingredient at the same time as drilling by inserting it in the same drill as the seeds. A suitable application rate is within the range of from 5 to 1000 g per hectare, more preferably from 10 to 500 g per hectare.

Alternatively the active compound can be applied directly to the plant by, for example, spraying or dusting either at the time when the fungus has begun to appear on the plant or before the appearance of fungus as a protective measure.

In both such cases the preferred mode of application is by foliar spraying. It is generally important to obtain good control of fungi in the early stages of plant growth as this is the time when the plant can be most severely damaged. The spray or dust can conveniently contain a pre- or post-emergence herbicide if this is thought necessary. Sometimes, it is practicable to treat the roots of a plant before or during planting, for example, by dipping the roots in a suitable liquid or solid composition. When the active compound is applied directly to the plant a suitable rate of application is from 0.025 to 5 kg per hectare, preferably from 0.05 to 1 kg per hectare.

Compounds of formula I where Z is O, W is 0 and R2 is H may be prepared by reacting a dialkyl malonate of formula II: Rl-CH(CO2Ra)(CO2Rb) (II) where R' is as defined hereinbefore and Ra and Rb are each alkyl, with an aminopyridine of the formula Ill

where X and p are as defined hereinbefore to give the corresponding compound of formula I.

Further compounds of formula I where W is 0 and Z is 0 may be prepared by 2 reacting a compound of formula I in which R2 is H in the presence of a base with a compound of formula R2Y where Y is a leaving group (e.g. chlorine, bromine, iodine or tosyloxy) and R2 is as defined hereinbefore but is other than hydrogen.

Further compounds of formula I may be prepared via compounds of formula IV

where R1, X and p are as defined hereinbefore, which may themselves be prepared by subjecting a compound of formula I where Z is O, W is 0 and R2 is H to the action of phosphoryl chloride or thionyl chloride.

For example, the compounds of formula I where W is O, S or NR3 and Z is 0 may be prepared by reacting a compound of the formula IV, where Z is 0, with a compound of formula R2QH, where R2 is as defined hereinbefore and Q is O, S or NR3 in the presence of a base.

Compounds of formula I where W is SO or SO2 may be prepared from the corresponding compounds where W is S by oxidation in known manner.

Compounds of formula I where Z is S may be prepared from the corresponding compounds where Z is O by reaction thereof with phosphorus pentasulfide in a known manner.

Compounds of formula ll are either known per se, or may be prepared in a manner known per se, for example as described in Chem Lett 1981, 367 or in Gazz Chim Ital, 1992, 122, 511, or in J. Org. Chem. 1986, 5112), 183 by reacting a halide of formula R1Hal where R1 is as defined hereinbefore with a malonate of formula RaOOC-CH2-COORb where Ra and Rb are as defined hereinbefore. Other compounds of formula ll may be prepared by methods analogous to those described in J. Am. Chem. Soc. 1946, 68, 1 934 by reacting an aromatic acetic acid derivative with diethyl carbonate or chloroform ate in the presence of a base.

Other methods will be apparent to the chemist skilled in the art as will be the methods for preparing starting materials and intermediates. The Examples also make apparent various methods of preparing compounds of the invention as well as starting materials and intermediates.

The invention is illustrated in the following Examples. Structures of isolated novel compounds were confirmed by NMR and/or other appropriate analyses.

Example 2-Amino-5-bromopyridine (1 g) and diethyl 3-thienylmalonate (2.8 g) were heated together overnight at 1800C under nitrogen. The mixture was then cooled and triturated with light petroleum (b.p. 40-60 C) to give 7-bromo-2-hydroxy 3-(3-thienyl)-4H-pyridoj 1 ,2-a]pyrimidin-4-one, m.p. > 3000 C.(Compound 1) Example 2 Compound 1 (1 g), 1-bromobutane (0.5 ml), potassium carbonate (0.64 g) and dry dimethylformamide (10 ml) were stirred together for 2 days. The mixture was then poured into water, acidified with hydrochloric acid, extracted with ether, washed with water and dried over magnesium sulfate.Purification using silica gel chromatography gave 7-bromo-2-butoxy-3-(3-thienyl)-4H-pyrido[1,2-a]pyrimidin4-one, m.p. 132-3 "C. (Compound 2) Example 3 2-Amino-5-bromopyridine (1 g) and diethyl phenylmalonate (3.11 mi) were heated together overnight at 1 8O0C under nitrogen, by when a dark orange solid had formed. This was cooled and triturated with petrol (40-600C) to give 7-bromo 2-hydroxy-3-phenyl-4H-pyrido! 1 ,2-a]pyrimidin-4-one, m.p. 305-6 0C. (Compound 3) Example 4 Compound 3 (1.3 g), 1-bromobutane (0.7 ml), potassium carbonate (0.89 g), and dry dimethylformamide (13 ml) were stirred for 2 days, and the mixture was then poured into water.The mixture was acidified with hydrochloric acid, extracted with ether, the extract washed well with water and dried over magnesium sulfate.

Purification using silica gel column chromatography gave 7-bromo-2-butoxy 3-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one, m.p. 91-3 C . (Compound 4) Examples Compound 4 (0.78 g), p-chlorophenylboronic acid (0.36 g), sodium carbonate (2M solution) (2.4 ml), toluene (5 ml), and tetrakis(triphenylphosphine)palladium (0.12 g) was heated at reflux overnight under nitrogen. The mixture was then cooled and diluted with ethanol (3 ml), and a solid was filtered off which was dissolved in dichloromethane, washed with 1M hydrochloric acid, dried over magnesium sulfate and treated with a small amount of charcoal.The mixture was filtered to give 7-(4-chlorophenyl)-2-butoxy-3-phenyl-4H-pyrido[1,2-a]pyrimidin4-one, m.p. 187-90C. (Compound 5) Example 6 p-Toluenesulfonyl chloride (11.4 g) was added portionwise with stirring and icecooling to Compound 3 (15.9 g) in dry pyridine (100 ml). The mixture was allowed to warm to room temperature and then stirred for half an hour. It was heated for 4 hours at 600C and allowed to stand at room temperature overnight. The mixture was added to a mixture of ice, hydrochloric acid and water, filtered and the solid which was collected was washed with water and ether and dried to give 7-bromo 3-phenyl-2-p-toluenesulfonyloxy-4H-pyrid 1 ,2-a]pyrimidin-4-one.

In a similar manner there was obtained 7-bromo-2-methanesulfonyloxy-3-phenyl 4H-pyrido[l,2-a]pyrimidin-4-one.

A mixture of 7-bromo-2-methanesulfonyloxy-3-phenyl-4H-pyrido[1,2-a]pyrimidin- 4-one (1.1 g) and piperidine (0.5 g) in dimethylformamide (15 ml) was heated with stirring at 80 OC for 2Y2 hours. The mixture was added to ice-water and extracted with ether. The extract was filtered and the filtrate washed with water, dried and evaporated. The residue was purified by silica gel chromatography to give 7-bromo-2-piperidino-3-phenyl-4H-pyrido[ 1 ,2-a]pyrimidin-4-one, m.p. 1 53-5 0C.

(Compound 6).

In a similar manner, 7-bromo-3-phenyl-2-p-toluenesulfonyloxy-4H-pyrido [1,2-a]pyrimidin-4-one and dimethylamine gave 7-bromo-2-dimethylamino-3-phenyl 4H-pyrido[l ,2-a]pyrimidin-4-one, m.p. 127-30. (Compound 6a) Example 7 Potassium t-butoxide (0.71 g) was added portionwise with stirring and cooling to butane-1-thiol (0.57 g) in dry dimethylformamide (15 ml) under nitrogen. The mixture was stirred for 1 5 minutes and then added slowly dropwise to 7-bromo 2-(2,4,6-trimethylbenzenesulfonyloxy-3-p 1 ,2-a]pyrimidin-4-one (2.5 g; obtained in a similar manner to the preparation of the starting materials of Example 6) in dry dimethylformamide (20 ml). The mixture was stirred at room temperature under nitrogen overnight. It was added to ice-water and extracted with ether.The extract was washed with water, dried, filtered and evaporated.

The residue was triturated with diisopropyl ether and filtered. The solid material was purified by silica gel chromatography to give 7-bromo-2-butylthio-3-phenyl 4H-pyrido[ 1 ,2-a]pyrimidin-4-one, m.p. 139-1 420C. (Compound 7) Example 8 A mixture of Compound 441 (see later; 1.5 g), sodium methoxide (0.73 g) and copper (I) iodide (0.17 g) in dry methanol (10 ml) and dry dimethylformamide (20 ml) was heated under reflux for 5 hours. The mixture was added to ice-water and extracted with dichloromethane. The extract was washed, filtered through kieselguhr, washed with water, dried and purified with charcoal and evaporated.

The residue was purified by silica gel chromatography to give 2,7-dimethoxy 3-phenyl-4H-pyrido[ 1 ,2-a]pyrimidin-4-one, m.p. 214-5 0C. (Compound 8) In a similar manner, Compound 477(see later), was treated with sodium metanethiolate to give 2,7-bis(methythio)-3-phenyl-4H-pyrido[ 1 ,2-a]pyrimidin- 4-one, m.p. 164-60C. (Compound 8a) Example9 Copper (I) cyanide (1.07 g) was added to a solution of Compound 2 (3.7 g) in dry dimethylformamide (8 ml). The mixture was heated under reflux for 4Y2 hours under nitrogen. Dilute ammonia (10 ml of 0.880 and ice water (20 ml)) and ether were added and the mixture stirred for 10 minutes.The mixture was filtered through kieselguhr and the ether solution separated, extracted with water and the ether extracts washed with water, dried and treated with charcoal and evaporated.

The residue was purified by silica gel chromatography to give 2-butoxy-7-cyano 3-phenyl-4H-pyrido[l ,2-a]pyrimidin-4-one, m.p. 95-7 0C. (Compound 9) Example 10 Sodium methoxide (0.16 g) was added to Compound 9 (0.95 g) in methanol (30 ml) at with stirring. The mixture was stirred at room temperature for 3 hours and allowed to stand overnight. The mixture was added to ice-water, acidified and filtered. The solid which was collected was washed with water and a little ether and dried to give 2-butoxy-7-[imino(methoxy)methyl]-3-phenyl-4H-pyrido- [1,2-a]pyrimidin-4-one, m.p. 135-6 OC. (Compound 10).

Example 11 A mixture of Compound 10 (0.47 g), hydrochloric acid (5 ml) and water (30 ml) was heated at 50 OC for 11/2 hours. The mixture was cooled and filtered and the solid which was collected washed with water and light petroleum and dried to give 2-butoxy-7-methoxycarbonyl-3-phenyl-4H-pyrido[ 1 ,2-ajpyrimidin-4-one, m.p. 93-40C. (Compound 11) The following compounds of the invention and intermediates were prepared in an analogous manner to one of the previous examples For the avoidance of doubt the numbering of the ring is shown. It will be seen that the nitrogen common to both rings is numbered in position 5

Cpd WR2 (X)p R1 m.p. (0C) 400 OH 7-Br 2-thienyl > 300 401 OBu 7-Br 2-thienyl 145-7 402 OH 7-Br 2CF3 Ph 310-2 403 OPr 7-Br 2CF3 Ph 158-60 404 OH 7-Br 20Me Ph 287-90 405 OH 7-Br 2,4 diFPh 320 406 OH 7-Br 2-pyridyl 252-4 407 OEt 7-Br Ph 152-7 408 OH 7-Br 3CIPh > 300 409 OH 7-Br 2C1,60Me Ph - > 300 410 OH 7-Br 2,4diCI Ph > 300 411 OH 7-Br 2-(2,5diCI-benzyloxy)-Ph 271-2 412 OPr 7-Br 20Me Ph 128-30 413 OPr 7-Br 2,4diFPh 141-3 414 OH 7-Br 2,6diCI Ph > 300 415 OH 7-Br 4CI,2N02 Ph > 300 416 OPr 7-Br 2,6diCI Ph 121-3 417 SCH2C02Me 7-Br Ph 156-8 418 OBu 7-Br 3-CIPh 109-10 419 OBu 7-Br 2-C1,6-OMePh 153-4 420 OBu 7-Br 2,4-diCIPh 145-7

Cpd WR2 (X)p R1 m.p. ( C) 421 OBu 7-Br 2-(2,5diCI-benzyloxy)-Ph 121-2 422 OH 7-Br 2-naphthyl > 300 423 SBut 7-Br Ph 227-9 424 OBu 7-Br 2-naphthyl 112-3 425 SPri H Ph 132-5 426 OH 7-Br 4-MePh 300-2 427 OBu 7-Br 4-MePh 136-8 428 OH 7-Br 4-CIPh > 300 429 OBu 7-Br 4-CIPh 122-4 430 OH 7-Br 2-MePh 283-5 431 OBu 7-Br 2Me Ph 101-3 432 OPr 7-Br 4C1,2N02 Ph 152-4 433 OBu 7-Br 2,6diCI Ph 166-9 434 OPr 7-Br Ph 137-9 435 Oallyl 7-Br Ph 97-8 436 Opentyl 7-Br Ph 146-8 437 OH 7-Br 4-OMePh 293 438 OCH2CONH2 7-Br Ph 230-2 439 OBu 7-Br 4-OMePh 128-30 440 OH 7-Br 4-BrPh > 320 441 OMe 7-Br Ph 181-3 442 OBu 7-Br 4-BrPh 127-9 443 OH 7-Cl Ph 293-4 444 OH H Ph 308-9 445 OH 7-N02 Ph 309-10 446 OBu 7-Cl Ph 83-4 447 OPr 7-Cl Ph 133-4 448 OEt 7-CI Ph 145-6 449 OMe 7-CI Ph 187-8 450 OH 7-Me Ph 315-6 451 OBu H Ph 84-5 452 OMe H Ph 140-1

Cpd WR2 (X)p R1 m.p. (OC) 453 OBu 7-N02 Ph 134-5 454 OBu 7-Me Ph 132-3 455 OEt 7-Me Ph 137-8 456 OH 7,9-C12 Ph 260-1 457 OPri 7-Br Ph 173-4 458 O(CH2)2Ph 7-Br Ph 141-2 459 OH 7,9-Br2 Ph 229-30 460 OH 7-Br 4-FPh 321-4 461 OH 7-Br 3-FPh 302-5 462 OBu5 7-Br Ph 73-4 463 OBu 7,9-Cl2 Ph 117-8 464 OPr 7,9-C12 Ph 131-2 465 OBu 7,9-Br2 Ph 115-6 466 OPr 7,9-Br2 Ph 142-3 467 OBu 7-Br 4-FPh 119-21 468 OPr 7-Br 4-FPh 130-2 469 OBu 7-Br 3-FPh 88-90 470 OEt 7-Br 3-FPh 140-2 471 OCH2SPh 7-Br Ph 133-6 472 OH 7-Br 2-FPh 294-7 473 OCH2cyclopropyl 7-Br Ph 129-31 474 OH 9-Br,7-Me Ph 237-8 475 OBu 9-Br,7-Me Ph 113-4 476 SPh 7-Br Ph 477 SMe 7-Br Ph 216-8 478 OBu 7-Br 2-FPh 112-4 479 0 Pr 7-Br 2-FPh 140-2 480 O-hexyl 7-Br Ph 87-9 481 O-decyl 7-Br Ph 60-2 482 OCH2C02Me 7-Br Ph 184-6

Cpd WR2 " R1 m.p. (OC)1 483 OCH2COBut 7-Br Ph 160-2 484 S-pyrimidin-2-yl 7-Br Ph 242-5 485 OBui 7-Br Ph 109-10 486 OCH2SiMe3 7-Br Ph 487 O-CH2CH=CH-CH-C#C-BUt 7-Br Ph 224-5 488 OPr 9-Br,7-Me Ph 138-9 489 OEt 9-Br, 7-Me Ph 146-7 490 OH 7-l Ph 300-1 491 OCH2-C(Me) = CH2 7-Br Ph 142-3 492 OCH2CH = CHC02Me 7-Br Ph 166-7 493 OCH2CH = CHMe 7-Br Ph 117-9 494 OCH2CH = CHCI 7-Br Ph 105-6 495 0-4-Butbenzyl 7-Br Ph 83-5 496 OEt 7-l Ph 169-70 497 OMe 7-SMe Ph 167-9 498 OH 9-Me Ph 272-5 499 OH 8-Me Ph 330(dec) 500 OCH2CH20Me 7-Br Ph 111-3 501 OCH2COPh 7-Br Ph 141-3 502 OCH2C-CH 7-Br Ph 223-5 503 Obenzyl 7-Br Ph 103-5 504 OBu 9-Me Ph 65-7 505 OPr 9-Me Ph 113-5 506 OBu 8-Me Ph 105-6 507 OEt 8-Me Ph 147-9 508 OCH2CN 7-Br Ph 157-9 509 OEt 6-Me Ph 95-7 510 O(CH2)2SMe 7-Br Ph 123-5 511 0-(4-OMebenzyl) 7-Br Ph 164-7 512 O-(4-OCF3benzyl) 7-Br Ph 127-9

Cpd WR2 (X)p R1 m.p. (0C) 513 OBu 7-1 Ph 118-9 514 OCH2CH=CMe2 7-Br Ph 144-5 515 O-(4-CNbenzyl) 7-Br Ph 212-4 516 1 \ 7-Br Ph 128-30 OCH2SS Cl 517 OCH2-imidazol-l-yl 7-Br Ph 104-5 518 O(CH2)2O(2,4,6-C13Ph) 7-Br Ph 185-6 519 Otosyl 7-Br H 144-59 520 OH 7-Br 4-pyridyl 319-22 521 OH 7-Br 3-pyridyl 308-11 522 OPri 9-Br,7Me Ph 140-1 523 OCH2cyclopropyl 9-Br,7-Me Ph 101-2 524 OBu 9-C1,7-CF3 Ph 44-8 525 OBu 7-Br 3-pyridyl 110-2 526 OPr 7-Br 3-pyridyl 129-31 527 OBu 7-Br 4 pyridyl 169-72 528 OEt 7-Br 4 pyridyl 154-6 529 OH 7-Br, 9-Me Ph 270(dec) 530 OH 6,8-Me2 Ph 234-6 531 OBu 7-Br,9-Me Ph 119-20 532 OPr 7-Br, 9-Me Ph 174-6 533 OBu 6-Me Ph 60-2 534 S-benzyl 7-Br Ph 145-6 535 NMe 7-Br Ph 198-200 533 OMe 7-Br H 148-9 539 OH 6-Me Ph 225-8 537 OBu 6,8-Me Ph 90-1 538 OPr 6,8-Me Ph 70-2 Test Example Compounds are assessed for activity against one or more of the following: Plasmopara viticola: vine downy mildew Erysiphe graminis f. sp. hordei: barley powdery mildew Erysiphe graminis f. sp. tritici: wheat powdery mildew Pyricularia oryzae: rice blast Botrytis cinerea: grey mould Venturia inaequalis: apple scab Leptosphaeria nodorum: glume blotch Pellicularia sasakii: rice sheath blight Aqueous solutions or dispersions of the compounds at the desired concentration, including a wetting agent, were applied by spray or by drenching the stem base of the test plants, as appropriate. Plants or plant parts were then inoculated with appropriate test pathogens and kept under controlled environment conditions suitable for maintaining plant growth and development of the disease. After an appropriate time, the degree of infection of the affected part of the plant was visually estimated.Compounds are assessed on a score of 1 to 3 where 1 is little or no control, 2 is moderate control and 3 is good to total control. At a concentration of 500 ppm (w/v) or less, the following compounds scored 2 or more against the fungi specified Plasmopara vltrcola 6a, 9, 10, 416-7, 423, 426, 428, 431, 436-8, 445, 453, 455, 458-9, 460-2, 465, 469, 473, 480, 516, 518-9.

Erysiohe aramtms f. sp. horde 2, 4, 412-3, 418 ENsrohe grammes f. sD. triticl 2, 9, 412-3, 418, 431, 434-7, 438-9, 441-2, 446-9, 451, 453-4, 457, 462-3, 465-70, 473-5, 477-82, 485-9, 491-6, 500, 502-3, 508-17, 519, 522-8, 531-2, 536.

Pyricula na oryzae 438, 475, 483, 490, 504-5.

Botrytis cinerea 509, 517, 536-7.

Venturia inaegualis 3, 413, 426, 432, 436, 491 Leotosphaeria nodorum 6, 410, 412, 443, 460, 470, 472, 474-5, 498, 500, 508, 511, 514-5 Pelliculana sasaku 435, 471, 525

Claims (2)

1. CLAIMS 1. The use in combating fungi of the substituted pyrido[l ,2-a]pyrimidinones of the formula I

   wherein R is an optionally substituted aryl or heteroaryl group; Z is O or S; W is O, S(O)n or NR3; R2 and R3, which may be the same or different, are each hydrogen or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group; each X, which may be the same as or different from any other X, is halogen, CN, NO2, SF5, acyl, O-acyl, trialkylsilyl, B(OH)2 or a group D, OD or S(O)nD where D is a group as defined herein before for R2 or is optionally substituted amino and n is 0, 1 or 2; or two adjacent groups X together with the atoms to which they are attached form a carbocyclic or heterocyclic ring; p is 0 to 4; and n is 0 to 2.
2. 2 Compounds of formula I as defined in claim 1 with the exception of the following compounds where Z is 0: B1 BZ 1X1, Ph OH 6-NH2 Ph OH 6-Me Ph OH 8-Me Ph OH Ph OH 9-OH Ph Oallyl Ph OCH2CH2NEt2- 4-OMePh OCH2CH2NEt2 4-OMePh OH