DESC:FIELD OF THE INVENTION
[0001] The present invention relates to synthesis of organic compounds, in particular to synthesis of insecticidally active compounds.

BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is a prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is a prior art.
[0003] Anthranilamide derivatives are an exceptionally active class of insect control compounds that selectively activates insect ryanodine receptors causing mortality from uncontrolled release of calcium ion stores in muscle cells. The control of invertebrate pests is extremely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer.
[0004] Anthranilamide derivatives like Chlorantraniliprole and Cyantraniliprole are insecticides of the ryanoid class. Chlorantraniliprole belongs to a class of selective insecticides featuring a novel mode of action to control a range of pests belonging to the order Lepidoptera and some other Coleoptera, Diptera and Isoptera species also having low mammalian toxicity and a favorable environmental profile. On the other hand Cyantraniliprole has activity against pests such as Diaphorinacitri that have developed resistance to other classes of insecticides.
[0005] Patent US 7,528,260 equivalent to IN298645 describes a process for preparing anthranilamide derivatives such as Chlorantraniliprole and Cyantraniliprole by condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and suitable substituted aminobenzamide derivative in presence of 3-picoline and methanesulfonyl chloride.
[0006] PCT publication WO2007/081553 describes a process for preparing Cyantraniliprole by condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and 2-Amino-5-cyano-N,3-dimethylbenzamide in presence of 3-picoline and methanesulfonyl chloride.
[0007] Prior art references such as US 8,871,939, US 8,748,630, US 8,153,844 and US 8,242279 each describe a process for preparing Chlorantraniliprole by condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and 2-Amino-5-chloro-N,3-dimethyl benzamide in presence of 3-picoline and methanesulfonyl chloride.
[0008] Prior art references such as US 8,247,570, US 8,049,029, US 8,212,075, US 8,034,968, WO2009/002810 and WO2008/069990 each describe a process for preparing Cyantraniliprole by condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and 2-Amino-5-cyano-N,3-dimethylbenzamide in presence of 3-picoline and methanesulfonyl chloride.
[0009] Patent US 8,217,179 equivalent to IN277502 describes a process for preparing anthranilamide derivatives such as Chlorantraniliprole and Cyantraniliprole by condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and suitable substituted aminobenzamide derivative in presence of pyridine and methanesulfonyl chloride.
[00010] CN102627629 describes condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and suitable substituted aminobenzamide derivative using phosphoryl chloride in presence of solvent acetonitrile.
[00011] Research papers such as Journal of Agricultural and Food Chemistry, 60(31), 7565-7572 (2012); Journal of Heterocyclic Chemistry, 53(4), 1036-1045 (2016); Molecular Diversity, 16(4), 711-725 (2012); Research on Chemical Intermediates, 39(7), 3071-3088 (2013), and Chinese Journal of Chemistry, 27(3), 579-586 (2009) each describe a process for preparing Chlorantraniliprole by condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and 2-Amino-5-chloro-N,3-dimethyl benzamide using oxalyl chloride in presence of N,N-dimethylformamide and dichloromethane.
[00012] Chinese patent CN108191822 discloses condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and 2-Amino-5-chloro-N,3-dimethyl benzamide by using 1-benzotriazolol and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl) in dichloromethane.
[00013] CN104844569 discloses condensation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid and 2-Amino-5-chloro-N,3-dimethyl benzamide by using N,N'-dicyclohexylcarbodiimide, N-hydroxysuccinimide in tetrahydrofuran.
[00014] The above-mentioned prior art processes suffer from one or other drawbacks like use of toxic or corrosive reagents, poor conversions, low yields, formation of byproducts and generation of high amounts of effluents making them economically non-viable. There is thus a need for a process which does not make use of corrosive or toxic chemicals, gives better conversion, is high yielding and leads to formation of low amounts of impurities and by-products.
[00015] The present invention satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior art.

OBJECTS OF THE INVENTION
[00016] An object of the present invention is to provide a new and improved process for preparing anthranilamide derivatives such as chlorantraniliprole and cyantraniliprole.
[00017] Another object of the present invention is to provide a process which allows to obtain anthranilamide derivatives in good yield, while minimizing formation of impurities.
[00018] Another object of the present invention is to provide a process for preparing anthranilamide derivatives which is simple to operate on a commercial scale, while reducing effluent production.
[00019] Other and further objects of this invention will be apparent from the following detailed description and appended claims which form a part of this specification.

SUMMARY OF THE INVENTION
[00020] The foregoing and other objects are attained by the present invention, which in one aspect provides a process for preparation of an anthranilamide derivative of Formula (I)

in which R1 represents chloro or cyano,
comprising reacting an anhydride compound of Formula (A) with an aminobenzamide compound of Formula (B)

in which R represents a C1 to C11 straight chain or branched alkyl, C3 to C7 cycloalkyl, C2 to C8 straight chain or branched alkene group having one or more unsaturation, methoxymethyl, ethoxymethyl, phenyl, or phenyl substituted with one or more substituents selected from the group consisting of C1 to C4 alkyl, amino, nitro, hydroxy, C1-2 alkoxy, chloro, bromo, cyano, SO3H and azide; and R1 is as defined above for Formula (I).
[00021] In one embodiment, the anthranilamide derivative of Formula (I) is chlorantraniliprole (when R1 is chloro).
[00022] In another embodiment, the anthranilamide derivative of Formula (I) is cyantraniliprole (when R1 is cyano).
[00023] In another aspect, the present invention is directed to a process for preparation of the compound of Formula (A) that can be used as an intermediate for the synthesis of insecticidally active compounds such as chlorantraniliprole and cyantraniliprole. In one embodiment of this aspect, the compound of Formula (A) can be prepared by a method as shown in Reaction-(1), which comprises reaction of a pyrazole derivative of Formula (II) with an acyl halide derivative of Formula (III),
wherein R is same as defined above, and X is chloro or bromo.
[00024] In another embodiment of this aspect, the compound of Formula (A) can also be prepared by a method as shown in Reaction-(2), which comprises reaction of a pyrazole carbonyl halide derivative of Formula (IV) with an acid derivative of Formula (V),

wherein R is same as defined above, and X is chloro or bromo.
[00025] In another embodiment of this aspect, the compound of Formula (A) can also be prepared by a method as shown in Reaction-(3), which comprises reaction of a pyrazole derivative of Formula (II) with an acid derivative of Formula (V),

wherein R is same as defined above.
[00026] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.

DETAILED DESCRIPTION OF THE INVENTION
[00027] The following is a detailed description of embodiments of the invention. The embodiments are in such detail as to clearly communicate the invention. However for a person skilled in the art, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present invention.
[00028] All numbers expressing quantities, percentages or proportions, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term "about."
[00029] It should be understood that the terms "a" and "an" as used herein refer to "one or more" of the enumerated components. It will be clear to one of ordinary skill in the art that the use of the singular includes the plural unless specifically stated otherwise. Unless otherwise stated, percentages in the present description are by weight.
[00030] In one aspect, the present invention provides a highly efficient process for preparation of an anthranilamide derivative of Formula (I),

in which R1 represents chloro or cyano,
comprising reacting an anhydride compound of Formula (A) with an aminobenzamide compound of Formula (B),

in which R represents a C1 to C11 straight chain or branched alkyl, C3 to C7 cycloalkyl, C2 to C8 straight chain or branched alkene group having one or more unsaturation, methoxymethyl, ethoxymethyl, phenyl, or phenyl substituted with one or more substituents selected from the group consisting of C1 to C4 alkyl, amino, nitro, hydroxy, C1-2 alkoxy, chloro, bromo, cyano, SO3H and azide; and R1 represents chloro or cyano.
[00031] The process according to the present invention has a number of advantages over the known processes for the preparation of anthranilamide derivatives such as chlorantraniliprole and cyantraniliprole. It enables to obtain anthranilamide derivatives of high purity. The process can be used to prepare anthranilamide derivatives of Formula (I) with a variety of possible substituents. In carrying out the process, reaction temperature and pressure are not critical. Pressure of reaction may vary from low sub-atmospheric pressures to high super-atmospheric pressures, and reaction temperature may vary from elevated temperatures up to reflux temperature. The process of the present invention is thus convenient to operate on a commercial scale.
[00032] In one embodiment, the anthranilamide derivative of Formula (I) is chlorantraniliprole (when R1 is chloro).
[00033] In another embodiment, the anthranilamide derivative of Formula (I) is cyantraniliprole (when R1 is cyano).
[00034] The compound of Formula (A) is a novel compound and hence forms another aspect of the present invention.
[00035] In yet another aspect, the present invention is directed to a process for preparation of compound of Formula (A) that can be used as an intermediate for the synthesis of insecticidally active compounds such as chlorantraniliprole and cyantraniliprole. In one embodiment of this aspect, the compound of Formula (A) can be prepared by a method as shown in Reaction-(1), which comprises reaction of a pyrazole derivative of Formula (II) with an acyl halide derivative of Formula (III). The Reaction-(1) may be performed in a solvent optionally in presence of a base and a catalyst, at a suitable temperature and pressure. The reaction product, i.e. compound of Formula (A) may be isolated or carried forward to next step in in-situ.

wherein R is as defined above, and X is chloro or bromo.
[00036] In another embodiment of this aspect, the compound of Formula (A) can be prepared by a method as shown in Reaction-(2), which comprises reaction of a pyrazole carbonyl halide derivative of Formula (IV) with an acid derivative of Formula (V). The Reaction-(2) may be performed in a solvent optionally in presence of a base and a catalyst, at a suitable temperature and pressure. The reaction product, i.e. compound of Formula (A) may be isolated or carried forward to next step in in-situ.

wherein R is as defined above, and X is chloro or bromo.
[00037] In another embodiment of this aspect, the compound of Formula (IV) can be prepared by a method known in the art by using thionyl chloride, thionyl bromide, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, oxalyl chloride, triphosgene or phosgene.
[00038] In another embodiment of this aspect, the compound of Formula (A) can be prepared by a method as shown in Reaction-(3), which comprises reaction of a pyrazole derivative of Formula (II) with an acid derivative of Formula (V). The Reaction-(3) may be performed in solvent in presence of a coupling agent and optionally in presence of a catalyst, at a suitable temperature and pressure. The reaction product, i.e. compound of Formula (A) may be isolated or carried forward to next step in in-situ.

wherein R is as defined above.
[00039] In an embodiment, the compound of Formula (A) is a compound of Formula (A-1):

Formula A-1
[00040] In an embodiment, the compound of Formula (A) is a compound of Formula (A-2):

Formula A-2
[00041] In an embodiment, the compound of Formula (A) is a compound of Formula (A-3):

Formula A-3
[00042] In an embodiment, the compound of Formula (A) is a compound of Formula (A-4):

Formula A-4
[00043] In an embodiment, the compound of Formula (A) is a compound of Formula (A-5):

Formula A-5
[00044] In an embodiment, the compound of Formula (A) is a compound of Formula (A-6):

Formula A-6
[00045] The compound of Formula (A) prepared by the process according to the present invention may be used as an intermediate for the synthesis of insecticidally active compounds. The use of compound of Formula (A) is a novel approach to the preparation of insecticidally active compounds such as chlorantraniliprole and cyantraniliprole. In various embodiments, the compound of Formula (A) according to the present invention, which is a novel compound not described in any prior art literatures, can be used for the synthesis of insecticidal compounds of Formula (I) according to Reaction-(4) shown below.

wherein R and R1 are as defined above.
[00046] In various embodiments, the compound of Formula (I) can be prepared in presence of a solvent and optionally in presence of a catalyst, at a temperature ranging from 0°C to 120°C, more preferably from 60°C to 110°C, and isolated from a reaction mixture by methods known in the art, such as crystallization, extraction or distillation.
[00047] In various embodiments, the compound of Formula (III) can be selected from the group consisting of 2-ethylacroloyl chloride, propenoyl chloride, pivaloyl chloride, cyclohexane carbonyl chloride, methoxyacetyl chloride, benzoyl chloride, benzoyl bromide, 4-nitrobenzoyl chloride, 4-isopropylbenzoyl chloride, 4-methoxybenzoyl chloride, 3,5-dinitrobenzoyl chloride, 3,4,5-trimethoxybenzoyl chloride and 2,4,6-trichlorobenzoyl chloride.
[00048] In various embodiments, the compound of Formula (V) can be selected from the group consisting of 2-ethylacrylic acid, propenoic acid, pivalic acid, cyclohexane carboxylic acid, methoxyacetic acid, benzoic acid, 4-nitrobenzoic acid, 4-isopropylbenzoic acid, 4-methoxybenzoic acid, 3,5-dinitrobenzoic acid, 3,4,5-trimethoxybenzoic acid and 2,4,6-trichlorobenzoic acid.
[00049] In various embodiments, the compound of Formula (B) is 2-amino-5-chloro-N,3-dimethylbenzamide when the compound of Formula (I) is chlorantraniliprole, or 2-amino-5-cyano-N,3-dimethylbenzamide when the compound of Formula (I) is cyantraniliprole.
[00050] In one embodiment, a molar ratio of compound of Formula (II) to the compound of Formula (III) in Reaction (1), or a molar ratio of compound of Formula (IV) to the compound of Formula (V) in Reaction (2), or a molar ratio of compound of Formula (II) to the compound of Formula (V) in Reaction (3) may range from 1: 0.5 to 1: 5.
[00051] In one embodiment, the solvent used in Reaction (1), (2), (3) and (4) is selected from the group consisting of methylene dichloride, ethylene dichloride, formic acid, acetic acid, dimethyl sulfoxide, N,N-dimethylformamide, carbon tetrachloride, chloroform, o-dichlorobenzene, chlorobenzene, toluene, tetrahydrofuran, acetone, methylisobutyl ketone, methyl-t-butylether, acetonitrile, hexane, ethyl acetate, methyl acetate, butyl acetate, cyclohexanone, pyridine, N-methyl-2-pyrrolidone, 1,2-dimethoxyethane, diglyme, 1,4-dioxane and mixture(s) thereof.
[00052] In various embodiments, each of the Reactions (1), (2) and (3) can be carried out at a temperature ranging from -10°C to reflux temperature.
[00053] In one embodiment, the base used in Reaction (1) and (2) is any suitable organic or inorganic base selected from triethylamine, pyridine, imidazole, benzimidazole, methylamine, N,N-dimethylformamide, picoline, ammonia, N-methylmorpholine, diisopropylethylamine, N,N-diethylamine, 2,6-lutidine, N-methyl-2-pyrrolidone, alkali or alkaline earth metal hydroxide, alkoxide, oxide, carbonate, bicarbonate and mixture(s) thereof. In one particularly preferred embodiment, the base used in Reaction (1) or (2) is triethylamine or N-methylmorpholine.
[00054] In one embodiment, the catalyst that can be used in Reaction (1), (2), (3) and (4) can be selected from any or a combination of 4-(dimethylamino)pyridine, N,N-dimethylformamide, pyridine, picoline, piperidine, 2,6-lutidine, hydroquinone, potassium iodide, BF3-etharate, acetic acid, 1-ethylpiperidine, phosphorus pentoxide, phosphoric acid, molecular sieves, (S)-binol, perchloric acid, 1-benzotriazolol, 4-methylbenzene sulfonic acid, iron metal, cupric oxide, cupric chloride, cuprous iodide, suitable lewis acid, 2,6-di-t-butyl-4-methylphenol (BHT), tetrabutyl ammonium bromide, tetrabutyl ammonium iodide and diethyl zinc. Preferably, the catalyst is 4-(dimethylamino) pyridine or 1-benzotriazolol.
[00055] In one embodiment, the coupling agent used in Reaction (3) can be selected from the group consisting of aluminum phosphate, aluminum oxide, burgess reagent, calcium oxide, cyanuric chloride, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N,N’-dicyclohexylcarbodiimide, ferric chloride, orthoformic acid, trifluoroacetic acid, phosphoric acid, phosphorus pentoxide, phosphoryl chloride, sulfuric acid and mixture thereof.
[00056] In one embodiment, Reaction (3) can be performed at reflux temperature in absence of any coupling agent.
[00057] In one embodiment, the base used in Reaction (1) and (2) can also work as catalyst according to suitability of reaction.
[00058] In one embodiment, catalyst used in Reaction (1), (2) or (3) is optional and the quantity of catalyst, if used, is in the range of 0.1 to 5 molar equivalent with respect to the compound of Formula (II) or the compound of Formula (IV).
[00059] In one embodiment, the Reaction (4) can be performed optionally in presence of a catalyst. If used, the catalyst should be present in an amount of from 0.1 to 5 molar equivalent with respect to the compound of Formula (A).
[00060] In one embodiment, molar ratio of compound of Formula (A) to the compound of Formula (B) used in Reaction (4) ranges from 1: 0.5 to 1: 5.
[00061] In another embodiment, a second solvent can be used in Reaction (4) for crystallization of compound of Formula (I), which can be selected from methanol, ethanol, propanol, hexane, heptane, toluene, chlorobenzene, isopropanol, n-butanol, t-butylalcohol, acetic acid, 1,4-dioxane, ethylene glycol, acetone, acetonitrile, ethyl acetate, methyl acetate, butyl acetate, xylene, petroleum ether, diethyl ether, N,N-dimethylformamide, methylisobutyl ketone, methyl-t-butylether, cyclohexane, water and mixture(s) thereof.
[00062] In another embodiment, Reaction (4) can be carried out at a temperature ranging from 0°C to 120°C, more preferably from 60°C to 110°C.
[00063] In various embodiments, sequence of adding reactants, reagent, solvent or catalyst as described in whole process steps can be interchanged according to suitability of reaction conditions.
[00064] In various embodiments, compound of Formula (I) produced in accordance with the process disclosed herein has a purity of greater than 97%, more preferably a purity of greater than 98.5% as determined by HPLC.
[00065] While the foregoing description discloses various embodiments of the invention, other and further embodiments of the invention may be devised without departing from the basic scope of the invention. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
[00066] The present invention is further explained in the form of following examples. However, it is to be understood that the foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.
Example 1: Preparation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic 2,2-dimethylpropanoic anhydride
[00067] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (10g, 0.032mol), ethylene dichloride (80ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10min and add triethylamine (4.6g, 0.045mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10min and add pivaloyl chloride (5.5g, 0.045mol) drop wise. After addition, stir the reaction mixture at 0-5°C for 1-2h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and distilled out the solvent from filtrate completely to obtain the title compound (12.58g) as cream coloured solid (Purity by HPLC >99%).
Example 2: Preparation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic 2,2-dimethylpropanoic anhydride
[00068] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (10g, 0.032mol), methylene chloride (80ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10min and add N-methylmorpholine (4.5g, 0.044mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10min and add pivaloyl chloride (5.5g, 0.045mol) drop wise. After addition, stir the reaction mixture at 0-5°C for 2h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and distilled out the solvent from filtrate completely to obtain the title compound (12.61g) as cream coloured solid (Purity by HPLC >98%).
Example 3: Preparation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic 2,2-dimethylpropanoic anhydride
[00069] Charged pivalic acid (5.75g, 0.056mol), o-dichlorobenzene (80ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 15min and add N-methylmorpholine (7.93g, 0.078mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10min and add 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carbonyl chloride (17.97g, 0.056mol). After addition, stir the reaction mixture at 0-5°C for 3h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and distilled out the solvent from filtrate completely to obtain the title compound (19.90g) as cream coloured solid (Purity by HPLC >97%).
Example 4: Preparation of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic 2,2-dimethylpropanoic anhydride
[00070] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (15g, 0.049mol), dimethylformamide (90ml) and N,N’-dicyclohexylcarbodiimide (6.8g, 0.033mol) into a RB flask and cool the reaction mass to 0°C. Stir the resulting reaction mixture for 1hr. Add pivalic acid (5.92g, 0.058mol) to the reaction mixture and stir for 3h at 0°C and 24h at room temperature. Monitor the reaction on HPLC and after completion of the reaction; filter the reaction mass and distilled out the solvent from filtrate completely to obtain the crude oily residue. The crude residue was treated with a solution of trifluoroacetic acid (40%) in methylene chloride. After 2h the solvent was removed to obtain title compound (13.80g) as cream coloured solid (Purity by HPLC >98%).
Example 5: Preparation of Chlorantraniliprole
[00071] In a RB flask, charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic 2,2-dimethylpropanoic anhydride (5g, 0.013mol) as obtained in previous examples and toluene (25ml) at room temperature to get a mixture. Further add 2-amino-5-chloro-N,3-dimethylbenzamide (2.58g, 0.013mol), 4-(dimethylamino)pyridine (1.58g, 0.013mol) at room temperature. Raise the temperature up to 110-115°C and stirred the reaction mixture for 3h. Monitor the reaction on HPLC. After completion of the reaction, distilled out toluene under vacuum at 45-50°C to obtain the thick mass. Add methanol (80ml) to the obtained mass and raise the temperature up to 60°C. Stir for 1h and then cool the mass to 0-5°C. Again stir for 2h at 0-5°C. After stirring, filter the solid and wash with chilled methanol (50ml) to obtain the crude solid. In another RBF charge crude solid and hexane (80ml) and then heat it at 60°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with hexane (50ml). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid. (4.09g) (Purity by HPLC 97.94%).
Example 6: Preparation of Cyantraniliprole
[00072] In a RB flask, charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic 2,2-dimethylpropanoic anhydride (5g, 0.013mol) as obtained in previous examples and toluene (25ml) at room temperature to get a mixture. Further add 2-amino-5-cyano-N,3-dimethylbenzamide (2.48g, 0.013mol), 4-(dimethylamino)pyridine (1.58g, 0.013mol) at room temperature. Raise the temperature up to 110-120°C and stirred the reaction mixture for 3h. Monitor the reaction on HPLC. After completion of the reaction, distilled out toluene under vacuum at 45-50°C to obtain the thick mass. Add methanol (85ml) to the obtained mass and raise the temperature upto 60°C. Stir for 1h and hen cool the mass to 0-5°C. Again stir for 2h at 0-5°C. After stirring, filter the solid and wash with chilled methanol (55ml) to obtain the crude solid. In another RBF charge crude solid and hexane (85ml) and then heat it at 60°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with hexane (55ml). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid. (3.7g) (Purity by HPLC 98.14%).
Example 7: Preparation of Chlorantraniliprole
[00073] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (60g, 0.196mol), methylene chloride (480ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10 min and add triethylamine (28g, 0.275mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10min and add pivaloyl chloride (33.5g, 0.275mol) drop wise. After addition, stir the reaction mixture at 0-5°C for 1-2 h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and wash with methylene chloride (50ml). Distilled out the solvent from filtrate completely to obtain the residue. Charge toluene (480ml) into the residue and stir for 5min. Transfer the resulting mixture in another RB flask. Charge 2-amino-5-chloro-N,3-dimethylbenzamide (39.3g, 0.196mol), 4-(dimethylamino)pyridine (24.2g, 0.196mol) and phosphorus pentoxide (56.2g, 0.392mol) at room temperature. Raise the temperature up to 105-110°C and stirred the reaction mixture for 3h. Monitor the reaction on HPLC. After completion of the reaction, cool the reaction mass to room temperature. Add water (600ml) and stir for 1h. Filter the solid and wash with water (180ml) and toluene (180ml) to obtain the crude solid. In another RBF charge crude solid and methanol (240ml) and then heat it at 60°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with methanol (120x2 ml). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid (58g) (Purity by HPLC 97.73%).
Example 8: Preparation of Chlorantraniliprole
[00074] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (3g, 0.01mol), methylene chloride (24ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10 min and add triethylamine (1.4g, 0.014mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10 min and add methoxy acetyl chloride (1.6g, 0.014mol) drop wise. After addition, stir the reaction mixture at 0-5°C for 1-2 h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and wash with methylene chloride (5ml). Distilled out the solvent from filtrate completely to obtain the residue having anhydride compound. Charge toluene (24ml) into the residue and stir for 5min. Transfer the resulting mixture in another RB flask. Charge 2-amino-5-chloro-N,3-dimethylbenzamide (2g, 0.010mol), 4-(dimethylamino) pyridine (1.2g, 0.010mol) and phosphorus pentoxide (2.8g, 0.020mol) at room temperature. Raise the temperature up to 105-110°C and stirred the reaction mixture for 2-3h. Monitor the reaction on HPLC. After completion of the reaction, cool the reaction mass to room temperature. Add water (30ml) and stir for 1h. Filter the solid and wash with water (9ml) and toluene (9ml) to obtain the crude solid. In another RBF charge crude solid and methanol (12ml) and then heat it at 60°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with methanol (6 ml x 2). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid (2.9g) (Purity by HPLC 98%).
Example 9: Preparation of Chlorantraniliprole
[00075] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (3g, 0.01mol), methylene chloride (24ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10 min and add triethylamine (1.4g, 0.014mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10 min and add cyclohexane carbonyl chloride (2.09g, 0.014mol) drop wise. After addition, stir the reaction mixture at 0-5°C for 1-2 h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and wash with methylene chloride (5ml). Distilled out the solvent from filtrate completely to obtain the residue having anhydride compound. Charge toluene (24ml) into the residue and stir for 5min. Transfer the resulting mixture in another RB flask. Charge 2-amino-5-chloro-N,3-dimethylbenzamide (2g, 0.010mol),4-(dimethylamino) pyridine (1.2g, 0.010mol) and phosphorus pentoxide (2.8g, 0.020mol) at room temperature. Raise the temperature up to 105-110°C and stirred the reaction mixture for 2-3h. Monitor the reaction on HPLC. After completion of the reaction, cool the reaction mass to room temperature. Add water (30ml) and stir for 1h. Filter the solid and wash with water (9ml) and toluene (9ml) to obtain the crude solid. In another RBF charge crude solid and methanol (12ml) and then heat it at 60°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with methanol (6 ml x 2). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid (3.1g) (Purity by HPLC 97.2 %).
Example 10: Preparation of Chlorantraniliprole
[00076] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (5g, 0.016mol), methylene chloride (40ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10 min and add triethylamine (2.3g, 0.023mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10 min and add 2, 4, 6-trichloro benzoyl chloride (5.78g, 0.023mol) drop wise. After addition, stir the reaction mixture at 0-5°C for 1-2 h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and wash with methylene chloride (10ml). Distilled out the solvent from filtrate completely to obtain the residue having anhydride compound. Charge toluene (40ml) into the residue and stir for 5min. Transfer the resulting mixture in another RB flask. Charge 2-amino-5-chloro-N,3-dimethylbenzamide (3.2g, 0.016mol), 4-(dimethylamino) pyridine (2g, 0.016mol) and phosphorus pentoxide (4.6g, 0.032mol) at room temperature. Raise the temperature up to 105-110°C and stirred the reaction mixture for 2-3h. Monitor the reaction on HPLC. After completion of the reaction, cool the reaction mass to room temperature. Add water (50ml) and stir for 1h. Filter the solid and wash with water (15ml) and toluene (15ml) to obtain the crude solid. In another RBF charge crude solid and methanol (20ml) and then heat it at 60°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with methanol (10 ml x 2). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid (4.7g) (Purity by HPLC 97.6 %).

Example 11: Preparation of Chlorantraniliprole
[00077] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (5g, 0.016mol), Ethylene dichloride (40ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10 min and add triethylamine (2.3g, 0.023mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10 min and add 4-methoxy benzoyl chloride (4g, 0.023mol). After addition, stir the reaction mixture at 0-5°C for 1-2 h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and wash with ethylene dichloride (10ml). Distilled out the solvent from filtrate completely to obtain the residue having anhydride compound. Charge toluene (40ml) into the residue and stir for 5min. Transfer the resulting mixture in another RB flask. Charge 2-amino-5-chloro-N,3-dimethylbenzamide (3.2g, 0.016mol), 4-(dimethylamino) pyridine (2g, 0.016mol) and phosphorus pentoxide (4.6g, 0.032mol) at room temperature. Raise the temperature up to 105-110°C and stirred the reaction mixture for 2-3h. Monitor the reaction on HPLC. After completion of the reaction, cool the reaction mass to room temperature. Add water (50ml) and stir for 1h. Filter the solid and wash with water (15ml) and toluene (15ml). In another RBF charge crude solid and methanol (20ml) and then heat it at 60°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with methanol (10 ml x 2). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid (4.8g) (Purity by HPLC 97.1%).
Example 12: Preparation of Chlorantraniliprole
[00078] Charged 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (3g, 0.01mol), methylene chloride (24ml) into a RB flask and cool the reaction mass to 0-5°C. Stir the resulting reaction mixture for 10 min and add triethylamine (1.4g, 0.014mol) drop wise at same temperature. Again stir the resulting reaction mixture for 10 min and add 3,4,5-trimethoxy benzoyl chloride (3.19g, 0.014mol). After addition, stir the reaction mixture at 0-5°C for 1-2 h and monitor the reaction on HPLC. After completion of the reaction, filter the reaction mass and wash with methylene chloride (5ml). Distilled out the solvent from filtrate completely to obtain the residue having anhydride compound. Charge toluene (24ml) into the residue and stir for 5min. Transfer the resulting mixture in another RB flask. Charge 2-amino-5-chloro-N,3-dimethylbenzamide (2g, 0.010mol), 4-(dimethylamino) pyridine (1.2g, 0.010mol) and phosphorus pentoxide (2.8g, 0.020mol) at room temperature. Raise the temperature up to 105-110°C and stirred the reaction mixture for 2-3h. Monitor the reaction on HPLC. After completion of the reaction, cool the reaction mass to room temperature. Add water (30ml) and stir for 1h. Filter the solid and wash with water (9ml) and toluene (9ml) to obtain the crude solid. In another RBF charge crude solid and isopropyl alcohol (12ml) and then heat it at 82°C for 1h. Cool the above reaction mass to 0-5°C and maintained for 2h. Filter the solid and wash with isopropyl alcohol (6 ml x 2). The resulting solid was dried under vacuum at 50-60°C to afford the title compound as white to off-white solid (3.1g) (Purity by HPLC 97.8%).
[00079] The numerical values of various parameters given in the specification are at approximations and slightly higher or slightly lower values of these parameters fall within the ambit and the scope of the invention.
[00080] While considerable emphasis has been placed herein on the specific steps of the preferred process, it will be highly appreciated that many steps can be made and that many changes can be made in the preferred steps without departing from the principles of the invention. These and other changes in the preferred steps of the invention will be apparent to those skilled in the art from the inventions herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.
[00081] The process according to the present invention have various advantages, such as:
i) The present invention provides a process having characteristics of economic and environment friendly with less effluent waste.
ii) The present invention process involves less expensive and readily available reagents and solvents.
iii) Solvents and catalyst used in present invention were less expensive and can be recovered and reused.
iv) Product of present invention is directly isolated from the reaction mass without involving any laborious work-up processes. Therefore, the process of the present invention is suitable for commercial scale.
v) The present invention provides a new process for preparing anthranilamide derivatives of compound of Formula (I), which involves efficient process resulting in competitive yield of the product with optimum purity at commercial scale with respect to the conventional prior art procedures.
vi) The present invention provides a process for preparing anthranilamide derivatives of compound of Formula (I), where unconverted intermediate(s) is recovered and recycled in further batches.
vii) The present invention provides a process for preparing anthranilamide derivatives of compound of Formula (I) that provides lower impurity profile in final product, as mild reaction condition restricts the formation of undesired impurities.
viii) The present invention provides a process that is simple, safe, time saving and having convenient operational steps at commercial scale.
ix) The present invention provides a process that saves utility at commercial scale because of simple work-up and product isolation procedure.
x) The present invention provides a process that improves productivity and equipment utilization at commercial scale.
xi) The present invention provides a process that is safe to people, animals, and the environment.
,CLAIMS:1. A process for preparation of an anthranilamide derivative of Formula (I)

wherein R1 is chloro or cyano,
comprising:
reacting an anhydride compound of Formula (A) with an aminobenzamide compound of Formula (B),

wherein R is a C1 to C11 straight chain or branched alkyl, C3 to C7 cycloalkyl, C2 to C8 straight chain or branched alkene group having one or more unsaturation, methoxymethyl, ethoxymethyl, phenyl, or phenyl substituted with one or more substituents selected from the group consisting of C1 to C4 alkyl, amino, nitro, hydroxy, C1-2 alkoxy, chloro, bromo, cyano, SO3H and azide; and
R1 is chloro or cyano.
2. The process as claimed in claim 1, wherein R1 is chloro.
3. The process as claimed in claim 1, wherein R1 is cyano.
4. The process as claimed in claim 1, wherein the reaction is carried out in a solvent and optionally in presence of a catalyst.
5. The process as claimed in claim 1, wherein the reaction is carried out at a temperature ranging from 0°C to 120°C.
6. The process as claimed in claim 1, wherein the compound of Formula (A) is prepared by a process comprising:
reacting a pyrazole derivative of Formula (II) with an acyl halide derivative of Formula (III)

wherein,
R is a C1 to C11 straight chain or branched alkyl, C3 to C7 cycloalkyl, C2 to C8 straight chain or branched alkene group having one or more unsaturation, methoxymethyl, ethoxymethyl, phenyl, or phenyl substituted with one or more substituents selected from the group consisting of C1 to C4 alkyl, amino, nitro, hydroxy, C1-2 alkoxy, chloro, bromo, cyano, SO3H and azide; and
X is chloro or bromo.
7. The process as claimed in claim 1, wherein the compound of Formula (A) is prepared by a process comprising:
reacting a pyrazole carbonyl halide derivative of Formula (IV) with an acid derivative of Formula (V)

wherein,
R is a C1 to C11 straight chain or branched alkyl, C3 to C7 cycloalkyl, C2 to C8 straight chain or branched alkene group having one or more unsaturation, methoxymethyl, ethoxymethyl, phenyl, or phenyl substituted with one or more substituents selected from the group consisting of C1 to C4 alkyl, amino, nitro, hydroxy, C1-2 alkoxy, chloro, bromo, cyano, SO3H and azide; and
X is chloro or bromo.
8. The process as claimed in claim 1, wherein the compound of Formula (A) is prepared by a process comprising:
reacting a pyrazole derivative of Formula (II) with an acid derivative of Formula (V)

wherein,
R is a C1 to C11 straight chain or branched alkyl, C3 to C7 cycloalkyl, C2 to C8 straight chain or branched alkene group having one or more unsaturation, methoxymethyl, ethoxymethyl, phenyl, or phenyl substituted with one or more substituents selected from the group consisting of C1 to C4 alkyl, amino, nitro, hydroxy, C1-2 alkoxy, chloro, bromo, cyano, SO3H and azide.
9. The process as claimed in any one of claims 6 to 8, wherein the reaction is carried out in a solvent and optionally in presence of a catalyst.
10. A compound of Formula (A)

wherein R is a C1 to C11 straight chain or branched alkyl, C3 to C7 cycloalkyl, C2 to C8 straight chain or branched alkene group having one or more unsaturation, methoxymethyl, ethoxymethyl, phenyl, or phenyl substituted with one or more substituents selected from the group consisting of C1 to C4 alkyl, amino, nitro, hydroxy, C1-2 alkoxy, chloro, bromo, cyano, SO3H and azide.
11. The compound of Formula (A) as claimed in claim 10, which is selected from the group consisting of:
, ,
Formula A-1 Formula A-2

, ,
Formula A-3 Formula A-4

, and
Formula A-5 Formula A-6