Title of Invention

"A PROCESS FOR PREPARING COMPOUNDS OF FORMULA IIA"

Abstract A process for preparing compounds of formula IIa comprising the steps of: a) reacting under basic conditions as herein defined, compounds of formula IV with compounds of formula V to give intermediates of formula VI, b) converting intermediates of formula VI to intermediates of formula VII by a process as herein defined, and c) converting intermediates of formula VII to compounds of formula IIa by a process as herein defined,
Full Text The present invention relates to 2-pyridylmethylamine compounds and salts thereof
(Formula Removed)
wherein A1 is a 2-pyridyl having substinients at the 3- and/or 5-position which are chosen independently from each other as being halogen; hydroxy; cyano; nitro; SF5; trialkylsilyl; an amino group optionally substituted by one or two E or acyl groups, each of which may be the same or different; acyl; a group E, OE or SE, where E is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, phenyl or heterocyclyl, each of which is optionally substituted by halogen, cyano, alkoxy, alkylthio, mercapto, hydroxy, nitro, amino, acyl, acyloxy, acylthio, phenyl, heterocyclyl, phenylthio, phenoxy, heterocyclyloxy or heterocyclylthio; or a group -C(E)=N-Q, where Q is E, OE, SE or an amino group optionally substituted by one or two E or acyl groups, each of which may be the same or different;
two adjacent substituents together with the atoms to which they are attached may form a ring which can contain up to 3 hetero atoms;
A2 is a phenyl which is optionally substituted with up to 5 substituents which are chosen independently from each other as being halogen; hydroxy; cyano; nitro; SF5; trialkylsilyl; an amino group optionally substituted by one or two E or acyl groups, each of which may be the same or different; acyl; a group E, OE or SE, where E is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, phenyl or heterocyclyl, each of which is optionally substituted by halogen, cyano, alkoxy, alkylthio, mercapto, hydroxy, nitro, amino, acyl, acyloxy, acylthio, phenyl, heterocyclyl, phenylthio, phenoxy, heterocyclyloxy or heterocyclylthio; or a group -C(E)=N-Q, where Q is E,

OE, SE or an amino group optionally substituted by one or two E or acyl groups,
each of which may be the same or different;
two adjacent substituents together with the atoms to which they are attached may
form a ring which can contain up to 3 hetero atoms;
L is -(C=O)-, SO2- or -(C=S)-; and
R1 and R2 are hydrogen.
Especially preferred substituents on the 2-pyridyl group (A1) are alkoxy, alkyl, cyano, halogen, nitro, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl and trifluoromethyl, particularly chlorine and trifluoromethyl.
The phenyl group A2 may have up to five substituents, preferably up to 3, especially up to two, which may be the same or different to each other.
Particularly preferred substituents are alkoxy, alkyl, halogen, nitro or trifluoromethyl. Preferably the linking group L is -(C = O)-.
The invention also includes any of the compounds specifically exemplified hereinafter.
Any alkyl group present in the molecule is preferably of 1 to 10 carbon atoms, especially of 1 to 7 carbon atoms, and particularly of 1 to 5 carbon atoms.
Any aikenyl or alkynyl group present in the molecule is preferably of 2 to 7 carbon atoms, for example allyl, vinyl or propargyl.
Any cycloalkyl cycloalkenyl or cycloalkynyl group present in the molecule is preferably of 3 to 7 carbon atoms, especially cyclopropyl, cyclopentyl, cyclohexyl or cyclohexenyl.
Substituents, when present on any alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl cycloalkynyi moiety may for example be halogen, cyano, optionally substituted alkoxy, optionally substituted alkylthio, mercapto, hydroxy, nitro, optionally substituted amino, acyl, acyloxy, acylthio, optionally substituted phenyl, optionally substituted heterocyclyt, optionally substituted phenylthio, optionally substituted phenoxy, optionally substituted heterocyclyloxy or optionally substituted heterocyclylthio.

Preferred substituents on any alkyl, alkenyl or alkynyl group are alkoxy. haloalkoxy or alkylthio, each containing 1 to 5 carbon atoms; halogen; or optionally substituted phenyl. An especially preferred group is trifluoromethyl.
Cycloalkyl. cycloalkenyl, cycloalkynyl groups may also be substituted by optionally substituted alkyl, alkynyl or alkenyl and vice versa.
Substituents when present on any phenyl or heterocyclyl group are preferably as defined above for substituents on A2.
The term heterocyclyl includes both aromatic and non-aromatic heterocyclyl groups. Heterocyclyl groups are generally 5, 6 or 7-membered rings containing up to 4 hetero atoms selected from nitrogen, oxygen and sulfur. Examples of heterocyclyl groups are furyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, dioxolanyl. oxazolyl, thiazolyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyranyl, pyridyl, pipendinyl, dioxanyl, morpholino, dithianyl, thiomorpholino, pyridazinyf, pyrimidinyl, pyrazinyl, piperazinyl, triazinyl. thiazolinyl, benzimidazolyi, tetrazolyl, benzoxazolyl, imidazopyridinyl, 1,3-benzoxazinyl, 1,3-benzothiazinyl, oxazolopyridinyl, benzofuranyl, quinolinyl, quinazolinyl, quinoxalinyl, sulfolanyl, dihydroquinazolinyl, benzothiazolyl, phthalimido, benzofuranyl, azepinyl, oxazepinyl, thiazepinyl, diazepinyl and benzodiazepinyl.
Amino groups may be substituted for example by one or two E or acyl groups, each of which may be the same or different, or two substituents together with the nitrogen to which they are attached can form a ring, preferably a 5 to 7-membered ring, which may be substituted and may contain other heteroatoms, for example rnorpholine, thiomorpholine, or pipendine. This ring can be substituted as for A.
The term acyl includes the residue of sulfur and phosphorus-containing acids as well as carboxylic acids. Examples of acyl groups are thus -COR5a, -COOR^3, -CXNR5aR6a, CON(R5a)OR6a, -COONR5aR6a, -CON(R5a)NR6aR7a, -COSR5a, -CSSR5a, S(O)yR5a, S(O)2OR5a, -S(O)yNR5aR6a, -P( = X)(OR5a)(OR6a), -CO-COOR5a. where R5a. R6a and R7a, which may be the same or different, are

hydrogen, optionally substituted alkyl,-optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkynyi optionally substituted phenyl or optionally substituted heterocyclyl, or R5a and R6a, or R6a and R7a, together with the atom(sl to which they are attached can form a-ring, y is 1 or 2 and X is O or S.
When substituted, substituents on the phenyl and alkyl groups are as defined above.
In preferred compounds of the invention
A1 is a mono- or dfsusbstituted 2-pyridyl group, substituted by chlorine and/or trifluoromethyl at the 3 and/or 5 position, e.g. 2-(3-chloro-5-trifluoromethyl) pyridyl; is -C(=O)-; and
R1 is hydrogen; and R2 is hydrogen
Particularly preferred substituents on the A2 phenyl are halogen.
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 (Pyncularia oryzae), cereal eyespot (Pseudocercosporella herpotrichcides], rice sheath blight (Pellicularia sasakii), grey mouid (Botrytis cinerea], damping off (Rhizoctonia solani], wheat brown rust (Puccinia recondite), late tomato or potato blight (Phytophthofa infestans], apple scab (Venturia inaequalis), glume blotch (Lepwsphaeria nodorum}. Other fungi against which the compounds may be active include other powdery mildews, other rusts, and general pathogens of Deuteromycete, Ascomycete, Phycomycete and Basidiomycete origin.

The invention thus also provides a fungicidal composition comprising 5 to 95% of a compound according to the invention in admixture with an agriculturally acceptable diluent or carrier.
The invention also provides a method of combating phytopathogenic fungi, at a locus infested or liable to be infested therewith, which comprises applying to the locus a compound of formula I and salts thereof
(Formula Removed)
wherein A1 is a 2-pyridyl which is substituted with up to four substituents which are chosen independently from each other as being halogen; hydroxy; cyano; nitro; SF5; trialkylsilyl; an ammo group optionally substituted by one or two E or acyl groups, each of which may be the same or different; acyl; a group E, OE or SE, where E is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, phenyl or heterocyclyl, each of which is optionally substituted by halogen, cyano, alkoxy, alkylthio, mercapto, hydroxy, nitro, amino, acyl, acyloxy, acylthio, phenyl, heterocyclyl, phenylthio, phenoxy, heterocyclyloxy or heterocyclylthio; or a group -C(E)=N-Q, where Q is E, OE, SE or an ammo group optionally substituted by one or two E or acyl groups, each of which may be the same or different;
two adjacent substituents together with the atoms to which they are attached may form a ring which can contain up to 3 hetero atoms;
A2 is a phenyl which is optionally substituted with up to 5 substituents which are chosen independently from each other as being halogen; hydroxy; cyano; nitro; SF5; trialkylsilyl; an amino group optionally substituted by one or two E or acyl groups,

each of which may be the same or different; acyl; a group E, OE or SE, where E is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, phenyl or heterocyclyl, each of which is optionally substituted by halogen, cyano, alkoxy, alkylthio, mercapto, hydroxy, nitro, amino, acyl, acyloxy, acylthio, phenyl, heterocyclyl, phenylthio, phenoxy, heterocyclyloxy or heterocyclylthio; or a group -C(E)=N-Q, where Q is E, OE, SE or an amino group optionally substituted by one or two E or acyl groups, each of which may be the same or different;
two adjacent substituents together with the atoms to which they are attached may form a ring which can contain up to 3 hetero atoms; L is -(C=O)-, -SO2- or -(C=S)-; R1 is-hydrogen, alkyl which is optionally substituted with alkoxy, haloalkoxy or alkylthio, each containing 1 to 5 carbon atoms, halogen, or phenyl; or acyl; and R2 is hydrogen or alkyl which is optionally substituted with alkoxy, haloalkoxy or alkylthio, each containing 1 to 5 carbon atoms, halogen, or phenyl.
Preferably the linking group L is -(C=O)-.
R1 is preferably hydrogen. When it is not hydrogen, it is preferably alkyl, optionally substituted by phenyl, or alkoxycarbonyl.
According to a further aspect of the invention, A1 is a 2-pyridyl group having substituents at the 3 and/or 5 position and no other position, R1 and R2 are hydrogen and A2 and 1, are as defined above.
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 aniomc 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 succmate. Nonionic agents include condensation products of fatty acid esters, fatty alcohols, fatty acid amides or fatty-alky!- or alkenyl-substituted phenols with ethyiene oxide, fatty esters of polyhydnc 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-Jinked amme prepared by the condensation of a carboxylic acid with a di-or 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, attapulgrte 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
ciay.
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 weigh;, 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 fcrm 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.
In addition, the compounds of the invention can be applied to plants or parts thereof which have been genetically modified to exhibit a trait such as fungal, insect, and/or herbicidal resistance.
The compounds of formula I may be obtained by reacting a compound of formula II, or its hydrochloride salt, with a compound of formula III according to Scheme 1, where X is a leaving group such as halogen. When L is -(C = O)- or -SO2.
preferred reaction conditions comprise mixing II with the corresponding benzoyl or sulfonyl chloride in the presence of triethylamine.

Scheme 1

(Formula Removed) II)
(Formula Removed) III)
(Formula Removed) (I)
Compounds of formula I where R2 is optionally substituted alky! can be prepared by alkylating in known manner, compounds of formula I where R2 is hydrogen.
Compounds of formula III are known or can be obtained in known manner.
Certain compounds of intermediate formula lla below, are known, i.e. compounds
of general formula II where R2 and R2 are hydrogen. However the art contains no high-yielding, preparative method for compounds of formula lla. We have now developed such a method.
Therefore, according to a third aspect, the invention provides a process for preparing compounds of formula lla comprising the steps of:
a) reacting under basic conditions, compounds of formula IV, with compounds of formula V to give intermediates of formula VI, ,Ra
(Formula Removed) (IV)
(Formula Removed) (V)
(Formula Removed) (VI)
b) converting intermediates of formula VI to intermediates of formula VII,

(Formula Removed) (VI)
(Formula Removed) (VII)
c) converting intermediates of formula VII to compounds of formula lla,
(Formula Removed) (VII)
(Formula Removed) (IIa)
wherein
Ra and Rb, which may be the same or different, are alkyl, alkenyl, alkynyl,
cycloalkyl, cycloalkenyl, heterocyclyl or phenyl, each of which may be substituted (preferably optionally substituted phenyl) or hydrogen;
E1 is both an electron withdrawing group and a group which may be replaced by hydrogen using methodology known to the skilled chemist in accordance with step c) (preferably a carboxy group or a carboxy ester group);
X1 is a leaving group (preferably halogen); and
A1 and R1 are as defined above for the first aspect of the invention.
Preferred basic conditions for step a) comprise reaction with an alkali metal hydride, alkoxide or carbonate.
Preferred, reaction conditions for step b) comprises treatment with dilute acid, particularly dilute hydrochloric acid.
When E1 is a carboxy group or carboxy ester group, suitable reaction conditions for decarboxylation [step c)] will be known to the skilled chemist. Preferred decarboxylation conditions comprise heating VII with dilute aqueous hydrochloric acid.
Compounds of formula IV are known or can be prepared in known manner.
Intermediates VI and VII may be isolated. Alternatively they may be generated in situ and the subsequent reaction step performed without isolation or purification. It is preferred that intermediate VI is generated in situ, whereas it is preferred that
intermediate VII is isolated.
Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers, but not the exclusion of any other integer or group of integers, including method steps.
The hydrochlonde salt of compounds of formula IIb, i.e. compounds of general formula II where R1 is optionally substituted alkyl and R2 is hydrogen, may be
prepared according to reaction Scheme 2. X2 is a leaving group such as bromine and the base is preferably potassium tert-butoxide. Preferred reaction conditions for conversion to the hydrochlonde salt of IIb is treatment with dilute hydrochloric acid.
Scheme 2
(Formula Removed)
Many of the compounds of formula lIb and their hydrochloride salts are novel. Therefore, according to a fourth aspect the invention provides a compound of formula lIb, and salts thereof,
(Formula Removed)
wherein A1 is as defined above and R1 is optionally substituted alkyl.
The 2-pyndyl group (A1) can have up to four substituents, preferably up to two, which may be the same or different to each other. Preferably, the substituents are on the 3 and/or 5 position of the 2-pyridyl group.
When substituted, preferred substituents on the 2-pyridyi group (A1) in formula lIb are halogen, hydroxy, cyano, nitro, SF5, trialkylsilyl, optionally substituted amino, acyl, or a group E, OE or SE, where E is alkyi, alkenyl, alkynyl, cycloalkyl, cycloalkenyl. phenyl or heterocyclyl, each of which is optionally substituted, or a group -C(E) =N-O, where O is E, OE, SE or optionally substituted ammo; or two adjacent substituents together with the atoms to which they are attached form an optionally substituted ring which can contain up to 3 hetero atoms. Especially preferred substituents are alkoxy, alkyl, halogen, nitro and trifluoromethyl, particularly chlorine and trifluoromethyl.
Preferably, A1 is a mono- or di-substituted 2-pyridyl group, substituted by chlorine and/or trifluoromethyl.
The invention is illustrated in the following Examples. Structures of isolated novel compounds were confirmed by NMR and/or other appropriate analyses.
Example 1
N-[(3-Chloro-5-trifluoromethyl-2-pyridyl)methyl]-α,α,α-trifluoro-o-toluamide
(Compound 1)
A solution of (3-chloro-5-trifluoromethyl-2-pyridyl)methylamine (0.35 g) in dry
ether (2 ml) was added to a solution of 2-trifluoromethylbenzoyl chloride (0.39 g)
and triethyiamine (0.27 ml) in dry ether (5 ml) and the mixture stirred overnight.
Water (20 ml) and ethyl acetate (10 ml) were added and the organic phase was
separated and washed with aqueous sodium hydrogen carbonate, dried and
evaporated under reduced pressure. The residue was purified by silica gel
chromatography to give the title product, m.p. 127-30°C.

Example 2
N-[(3-Chlpro-5-trifluoromethyl-2-pyridyl)methyl|-N-methyl-2,6-dichlorobenzamide (Compound 63)
Sodium hydride (0.077 g of a 60% dispersion in oil) was added, with stirring, to a solution of compound 21 (see in table below) in dry tetrahyorofuran and under nitrogen at room temperature. The mixture was warmed to 30°C and after 10 minutes was stirred at room temperature for 30 minutes. Methyl iodide (0.12 ml) was added and the mixture stirred at room temperature overnight. The mixture was quenched by the addition dropwise of a solution of methanol in tetrahydrofuran followed by water. The tetrahydrofuran was removed by evaporation under reduced pressure and the residue was partitioned between water and ether The aqueous layer was extracted twice with ether and the combined extracts were washed with water and then brine and dried. The extract was evaporated under reduced pressure to give the title product, m.p. 83-4°C.
Example 3
N-[(3.5-dichloro-2-pyridyl)methyl)-2,6-dichlorobenzamide (Compound 59) To-a stirred solution of the product from stage b) (see below) (0.30 g) and tnethylamine (0.4 ml) in tetrahydrofuran (5 ml) was added 2,6-dichlorobenzoyl chloride (0.2 ml) dropwise at room temperature, and stirring was continued for 12 hours. The reaction mixture was concentrated, water was added (10 ml) and the mixture was stirred for 1 5 minutes. The mixture was filtered and the resulting solid washed with water and then with light petroleum (b.p. 40-60°C). The solid was recrystallised from diisopropyl ether to give the title product, m.p. 161-5°C.
Preparation of Starting Materials
a) Ethyl 2-P,5-dichloro-2-pyridyl)glycinate
To a stirred solution of sodium hydride (0.445 g) in dry dimethylformamide (4 ml) at 0°C was added ethyl N-(diphenylmethy!ene)glycinate (1.485 g) in dry dimethylformamide (3 ml) and stirring was continued for 20 minutes. 2.3,5 Trichloropyridine (1.58 g) in dry dimethylformamide (4 ml) was then added dropwise over 10 mins at 5°C and the reaction mixture was stirred for 2 hours at room temperature. 2M hydrochloric acid (25 ml) was added and stirring continued for 2 hours. The solution was washed with diethyl ether and the layers were separated. The aqueous phase was neutralised

with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine (x2), dried (MgSO4), filtered and the solvent removed to leave a residue which was purified by silica gel chromatography eluting with ethyl acetate/light petroleum (4O-60°C) to give the title product.
b) l3.5-Dichloro-2-pyridyl)methylamine hydrochloride
A mixture of the product from stage a) (0.24 g) and 3M hydrochloric acid (20 ml) was heated under reflux for 4 hours. On cooling the mixture was washed with diethyl ether and the layers separated. Water was removed from the aqueous phase by azeotropic evaporation with toluene (x3) to give the title product.
Example 4
N-[ 1-(3-Chloro-5-triflupromethyl-2-pyridyl)-2-phenylethyl]-2.6-dichlorobenzamide
(Compound 83)
To a solution of the product from stage c) (see below) (0.31 g) in dichloromethane
(10 ml) was added triethylamine (0.28 ml) followed by 2,6-dichlorobenzoyl chloride (0.15 ml). The mixture was stirred at room temperature for 1.5 hours and then evaporated to dryness. Diethyl ether (20 ml) was added and the solution was washed with 2M hydrochloric acid (10 ml), then water (10 ml), then sodium bicarbonate solution (10 ml) followed by water (10 ml). The organic layer was separated, dried (MgSO4) and the solvent removed. The residue was purified by
silica gel chromatography [light petroleum (b.p. 40-60°C):diethyl ether (1:1)] to give the title product as a solid, m.p. 1 64-8°C.
Preparation of starting materials
a) N- [(3-chloro-5-trifluoromethyl-2-pyridynmethyl]benzophenone imine.
To a solution of benzophenone imine (1.67 ml) in dry dichloromethane (25 ml) at 10°C was added (3-chloro-5-trifluoromethyl-2-pyridyl)methylamine hydrochloride (2.47 g). The solution was stirred at room temperature for 3 hours and then filtered. The filtrate was evaporated to dryness and purified by silica gel chromatography [light petroleum/diethyl ether (4:1)] to give the title product

b) N-[ 1 -(3-Chloro-5-trifluoromethyl-2-pyridyl)-2-phenylethyl]benzophenone
imme
To .1 solution of potassium tetr-butoxide (0.33 g) in tetrahydrofuran (5 ml) at -60°C was added the product from stage a) in tetrahydrofuran (10 ml). After stirring at -60°C for 10 minutes, benzyl bromide (0.36 ml) in dry tetrahyarofuran (20 ml) was added dropwise at -50°C. The solution was allowed to slowly attain room temperature and stirring continued overnight. The mixture was evaporated to dryness and diethyl ether (35 ml) and acetic acid (2 ml) were added. The mixture was washed with water (3x10 ml) and the phases were separated. The organic phase was dried (MgSO4) and the
solvent removed to give the title product.
c) 1 -(3-Chloro-5-trifluoromethyl-2-pyridyl)-2-phenylethylamine hydrochlonde
To a solution of the product from stage b) (1.29 g) in diethyl ether (5 ml) was added 1M hydrochloric acid (10 ml) at room temperature and the solution was stirred at room temperature for 2 hours. The mixture was filtered to give a solid, which was washed with water (1 5 mi) then ether (1 5 ml). Drying in vacuo gave the title product. Water was removed from the aqueous phase by azeotropic distillation with toluene (x3), to give further quantities of the title product.
In a similar manner to one of the previous Examples, the following compounds of general formula ia were obtained. The table includes the compounds described in the previous Examples

(Formula Removed)
(la)
Table1

(Table Removed)
Example 5
/V-[1-(3-Chioro~5-tnfluoromethyl-2-pyridyl)-2,4-dichIprobenzenesulfonamide (Compound 501)
Triethylamme (0.28 ml) was added to a suspension of (3-chloro-5-trifluoromethyl-2-pyridyl)methylamine hydrochloride (0.25 g) in tetrahydrofuran (6 ml). After 15 minute, the white suspension was filtered and washed with tetrahydrofuran. The filtrate and washings were added to 2,4-dichlorobenzenesulfonyl chloride (0.25 g) and the mixture stirred overnight at room temperature, water added and stirred for 30 minutes. The white solid, which formed, was collected. This was the title product, m.p. 125-6°C (Compound 501)
In a similar manner, the following compounds of general formula la were obtained. The table includes the compound described in the previous Example.
(Formula Removed)
(Table Removed)
Example 6
Ethyl 2-(3-chloro-5-trifluoromethyl-2-pyridyl)-N-(3,4-dimethoxybenzoyl)glycinate
(Compound 601)
Triethylamine (0.28 ml) was added to a solution of ethyl 2-(3-chloro-5-trifluoromethyl-2-pyridyl)glycinate (1 g; prepared in a similar manner to the starting material for Example 3) in dimethylformamide (10 ml) with stirring followed by 3,4-dimethoxybenzoyl chloride (0.70 g). the mixture was stirred for 45 minutes and evaporated. The residue was extracted with ethyl acetate and the extracts worked up to give the title product, m.p. 40-3°C. (Compound 601)
In a similar manner to one of the previous Examples, the following compounds in Table 3 of general formula Ic were obtained. The table includes the compound described in the previous Example.

(Formula Removed) (Ic)
Table 3

(Table Removed)
Example 7
N-[(3-Chloro-5-trifiuoromethyl-2-pyridyl)methyl]-2-chlorobenzenethioamide (Compound 701)
A solution of compound 23, (3.84 g) and Lawesson's reagent (4.45 g) in toluene (50 ml) was heated at 80°C for I hour. The mixture was purified by silica gel chromatography to give to give the title compound, m.p. 102-3°C.
In a similar manner the following compounds were obtained. The table includes the compound described in the previous Example.
(Formula Removed)
(Table Removed)
Test Example
Compounds are assessed for activity against one or more of the following:
Phytophthora infestans: late blight
Plasmopara viticola: vine downy mildew
Erysiphe graminis f. sp. tritici: wheat powdery mildew
Pyncularia oryzae: rice blast
Leptosphaeria nodorum: glume blotch
Botrytis cinerea: grey mould
An aqueous solution of the compound at the desired concentration, including a wetting agent, was applied by spray or by drenching the stem base of the test plants, as appropriate. After a given time, plants or plant parts were inoculated with appropriate test pathogens before or after application of the compounds as appropriate, and kept under controlled environmental 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. The compound was 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 compound scored 2 or more against the above fungi.
Phytophthora infestans
1, 3, 6, 8, 13, 14, 17-21, 22, 23, 25, 27, 29, 31-34, 37-46, 59, 62-64, 66, 68-71, 85, 87, 95, 98, 101, 107, 110, 122-124, 128, 130, 132, 171, 173, 180 and 701.
Plasmopara viticola
1, 3, 13, 14, 15, 17-21, 22, 23, 25, 27, 29, 31-34, 37, 39, 41-46, 59, 63, 64, 66, 69, 7l, 84, 86, 87, 102-110, 124, 128, 130, 132, 150 and 171. Erysiphe graminis f. sp. tritici
16, 25, 28, 146, 147, 148, 151, 155, 156, 165, 150 and 151. Pyricularia oryzae
16, 25, 31, 38, 41, 45, 65, 89. 97, 146, 157, 169, 150, 151, 152, 156, 158 and 176.
Leptosphaeria nodorum
15, 16, 18, 22, 33, 34, 92, 63. 128, 130, 143, 149 and 150. Botrytis cinerea 127,130,134 and 139






We claim
1. A process for preparing compounds of formula IIa
(Formula Removed)
comprising the steps of:
a) reacting under basic conditions as herein defined, compounds of formula IV with compounds of formula V to give intermediates of formula VI,
(Formula Removed)
b) converting intermediates of formula VI to intermediates of formula VII by a process as herein defined,
(Formula Removed)
And
c) converting intermediates of formula VII to compounds of formula Iia by a process as herein defined,
(Formula Removed)
wherein
Ra and Rb, which may be the same or different, are alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl or phenyl, each of which is unsubstituted or substituted by halogen, cyano, alkoxy, alkylthio, mercapto, hydroxy, nitro, amino, acyl, acyloxy, acylthio, phenyl, heterocyclyl, phenylthio, phenoxy, heterocyclyloxy or heterocyclylthio;
E1 is a carboxy group or a carboxy ester group;
X1 is a halogen atom; and
A1 is a 2-pyridyl having substituents at the 3- and/or 5-position which are chosen independently from each other as being halogen; hydroxy; cyano; nitro; SF5; trialkylsilyl; an amino group which is unsubstituted or substituted by one or two E or acyl groups, each of which may be the same or different; acyl; a group E, OE or SE; or a group -C(E)=N-Q, where Q is E, OE, SE or an amino group which is unsubstituted or substituted by one or two E or acyl groups, each of which may be the same or different;
E is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, phenyl or heterocyclyl, each of which is unsubstituted or substituted by halogen, cyano, alkoxy, alkylthio, mercapto, hydroxy, nitro, amino, acyl,
acyloxy, acylthio, phenyl, heterocyclyl, phenylthio, phenoxy,
heterocyclyloxy or heterocyclylthio; and
alkyl groups have 1 to 10 carbon atoms; alkenyl and alkynyl groups have 2 to 7 carbon atoms; cycloalkyl, cycloalkenyl and cycloalkynyl groups have 3 to 7 carbon atoms and heterocyclyl groups are 5, 6 or 7 membered rings containing up to 4 hetero atoms selected from nitrogen oxygen and sulfur.
2. A process as claimed in claim 1, wherein Ra and Rb, which may be the same or different, represent phenyl which is unsubstituted or substituted by halogen, cyano, alkoxy, alkylthio, mercapto, hydroxy, nitro, amino, acyl, acyloxy, acylthio, phenyl, heterocyclyl, phenylthio, phenoxy, heterocyclyloxy or heterocyclylthio.
3. A process as claimed in claim 1 or claim 2, wherein the 2-pyridyl group A1 is
substituted with alkoxy, alkyl, cyano, halogen, nitro, alkoxycarbonyl,
alkylsulfinyl, alkylsulfonyl or trifluoromethyl.
4. A process as claimed in claim 3, wherein the 2-pyridyl group A1 is substituted
with chlorine and/or trifluoromethyl.
5. A process as claimed in claim 4, wherein the 2-pyridyl group A1 is 2-(3-chloro-5-trifluoromethyl) pyridyl.

Documents:

4639-DELNP-2007-Abstract-(12-09-2011).pdf

4639-delnp-2007-assignment-(26-09-2007).pdf

4639-DELNP-2007-Claims-(12-09-2011).pdf

4639-delnp-2007-claims.pdf

4639-DELNP-2007-Correspondence Others-(12-09-2011).pdf

4639-DELNP-2007-Correspondence Others-(18-08-2011).pdf

4639-delnp-2007-correspondence-others-1.pdf

4639-delnp-2007-correspondence-others.pdf

4639-delnp-2007-description (complete).pdf

4639-DELNP-2007-Form-1-(12-09-2011).pdf

4639-delnp-2007-form-1.pdf

4639-DELNP-2007-Form-13-(12-09-2011).pdf

4639-delnp-2007-form-18.pdf

4639-DELNP-2007-Form-2-(12-09-2011).pdf

4639-delnp-2007-form-2.pdf

4639-DELNP-2007-Form-3-(18-08-2011).pdf

4639-delnp-2007-form-3.pdf

4639-delnp-2007-form-5.pdf

4639-DELNP-2007-GPA-(12-09-2011).pdf

4639-delnp-2007-gpa-(26-09-2007).pdf

4639-DELNP-2007-Petition-137-(12-09-2011).pdf


Patent Number 256043
Indian Patent Application Number 4639/DELNP/2007
PG Journal Number 17/2013
Publication Date 26-Apr-2013
Grant Date 23-Apr-2013
Date of Filing 18-Jun-2007
Name of Patentee BAYER CROPSCIENCE LIMITED
Applicant Address BRITISH BODY CORPORATE, OF HAUXTON, CAMBRIDGE CB2 5HU, UK,
Inventors:
# Inventor's Name Inventor's Address
1 DAVID HARDY CHESTERFORD PARK, SAFFRON WALDEN, ESSEX CB10 1XL,U.K.
2 ELIZABETH ANNE SAVILLE CHESTERFORD PARK, SAFFRON WALDEN, ESSEX CB10 1XL,U.K.
3 BRIAN ANTHONY MOLONEY CHESTERFORD PARK,SAFFRON WALDEN, ESSEX CB10 1XL, U.K.
PCT International Classification Number A01N 43/40
PCT International Application Number PCT/GB99/00304
PCT International Filing date 2000-08-17
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 9817353.7 1998-08-11 U.K.
2 9803413.5 1998-02-19 U.K.
3 9813998.3 1998-06-30 U.K.