DESC:Field of the Invention
The present invention relates to an improved process of preparation of carboxamide derivatives. More particularly, the present invention relates to an improved process of preparation of Cyantraniliprole of Formula I.

Background of the Invention
Cyantraniliprole 3-bromo-1-(3-chloropyridin-2-yl)-N-(4-cyano-2-methyl-6-(methylcarbamoyl)phenyl)-1H-pyrazole-5-carboxamide of Formula I is an insecticide belonging to the anthranilic diamide class of chemistry and is intended for the control of Lepidopteran, Coleopteran, and some Dipteran pests in commercial agriculture on both perennial and annual crops.

Formula I

A number of processes for the preparation of Cyantraniliprole are already known from the literature. CN patent no. CN117186060 provides a process for preparation of Cyantraniliprole by using acid chloride reagent thionyl chloride, oxalyl chloride, triphosgene; in a second stage 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid and 2-amino-5-cyano-N,3-dimethylbenzamide coupled in a solvent with an organic base, such as 3-picoline, pyridine, 2-picoline and trimethylamine.

The above process has disadvantages as it involves the use of organic base like pyridine, picoline etc, which are hazardous to environment, high volume of aqueous and organic waste are generated during the process. Also, the process uses reagent such as triphosgene, oxalyl chloride which is not only expensive but also hazardous to environment.

PCT publication no. WO2021249396, discloses a process of preparation of Cyantraniliprole by reacting 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, with thionyl chloride in a solvent selected from acetonitrile, dioxane, THF, mixtures thereof, to obtain 3-bromo-l-(3-chloro- 2-pyridinyl)-1 H-pyrazole-5-carboxylic acid chloride, thereafter, solvent is distilled out and reaction mass is reacted with 2-amino-5-cyano-N,3-dimethylbenzamide, in the presence of acetonitrile, DMF or mixtures thereof to obtain product. The above process has disadvantages as it involves the use of distillation/azeotropic distillation which reduces the productivity at large scale.

PCT publication nos. WO2019207595 and WO2023095161, discloses a process of preparation of Cyantraniliprole by reacting 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid, with thionyl chloride in a toluene, to obtain 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carbonyl chloride. Thereafter, 2-amino-5-cyano-N,3-dimethylbenzamide in toluene is reacted with 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carbonyl chloride in the presence of organic base like 3-Picoline to obtain Cyantraniliprole, the use of organic base like 3-Picoline is harmful to environment further yield is also low.

Hence, there is a need in the art to provide an improved process of preparation of Cyantraniliprole which is simple, cost-effective, improves yield and purity on a commercial scale.

Summary of the Invention
Accordingly, the present invention provides a process of preparation of Cyantraniliprole of Formula I,

Formula I
said process comprising the steps of:
a) reacting 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid, with a chlorinating agent in a suitable solvent to obtain 3-bromo-1-(3- chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride,
b) reacting the 3-bromo-1-(3- chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride with 2-amino-5-cyano-N, 3-dimethylbenzamide, in presence of an inorganic base in a suitable solvent to obtain Cyantraniliprole of Formula-I,
c) isolating the compound of formula-I.

Detailed description of the Invention
The present invention provides an improved process of preparation of Cyantraniliprole of Formula I.

Formula I
said process comprising the steps of:
a) reacting 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid, with a chlorinating agent in a suitable solvent to obtain 3-bromo-1-(3- chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride,
b) reacting the 3-bromo-1-(3- chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride with 2-amino-5-cyano-N, 3-dimethylbenzamide, in presence of an inorganic base in a suitable solvent to obtain Cyantraniliprole of Formula-I,
c) isolating the compound of formula-I.

In an embodiment, 3-bromo-1-(3- chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride, may be isolated in step a). In an alternative embodiment, step a) and step b) are carried out insitu.

In another embodiment, the chlorinating agent used in step a) is selected from Thionyl chloride (SOCl2), Oxalyl chloride (COCl)2, Cyanuric chloride, Phosphorus oxychloride, Phosphorus trichloride, Phosphorus pentachloride etc.

In another embodiment, in step a) optionally the reaction is carried out in the presence of catalytic amount of N, N-Dimethylformamide (DMF).

The suitable solvent used in step a) is selected from toluene, acetonitrile, methylene chloride chloroform, xylene, methyl ethyl ketone, benzene, dioxane, hexane, carbon tetrachloride, and tetrahydrofuran, dichloromethane, bromodichloromethane, dibromochloromethane, trichlorofluoromethane, 1,1-dichloroethane, 1,2- dichloroethane (ethylene dichloride), 1,1,1-trichloroethane, 1,12-trichloroethane, 1,1,2,2- tetrachloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethylene, trans-1,2- dichloroethylene, trichloethylene or mixtures thereof. Hydrocarbon solvents such as cyclohexane, heptane, mixtures thereof.

The mole equivalents of chlorinating reagent used in step a) are 1.0 to 2.0, preferably 1.2 to 1.5 mole equivalents and more preferably 1.0 to 1.3 mole equivalents with respect to 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid.

In step (a), the reaction may be performed from 25°C to 125°C for 1 hour to 12 hours, preferably 40-80°C for 1 hour to 5 hours. The obtained 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride may be used in the next reaction directly without isolation.

In an embodiment, in step b) 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride reacts with 2-amino-5-cyano-N, 3-dimethylbenzamide, in presence of an inorganic base in a suitable solvent to obtain Cyantraniliprole of formula-I.

The inorganic base used in step b) is selected from sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide, lithium carbonate, magnesium carbonate, magnesium hydroxide, cesium carbonate, calcium carbonate, calcium hydroxide or mixtures thereof, preferably sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate.

The suitable solvent used in step b) is organic solvents, for example polar aprotic solvent comprises acetonitrile, dimethylformamide, tetrahydrofuran, ethyl acetate, acetone, dimethylsulfoxide or mixture thereof. The chlorinating solvent comprises dichloromethane, chloroform, bromodichloromethane, dibromochloromethane, trichlorofluoromethane, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane (ethylene dichloride), 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, trichloethylene or mixture thereof. Hydrocarbon solvents such as cyclohexane, hexane, heptane, toluene, xylene or mixtures thereof.

In an embodiment, the mole equivalents of 2-amino-5-cyano-N, 3-dimethylbenzamide used in step b) are 0.9 to 1.2 with respect to 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid.

In a preferred embodiment, the solvent used in step b) is selected from ethylene dichloride or dichloromethane or a mixture of ethylene dichloride + water or a mixture of dichloromethane + water. The ratio of ethylene dichloride + water or dichloromethane + water is 15:0.5, preferably is in the range of 4:0.5 and more preferably is in the range of 3:0.5.

In an embodiment, the mole equivalents of inorganic base used in step b) are 0.4 to 2.5, preferably 1.4 to 2.5 mole equivalents with respect to 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid.

In an embodiment, in step b), the reaction may be performed from 0°C to 90°C for a time period in the range of 1 hour to 60 hours, preferably 30 to 80°C for 2 hour to 10 hours.

In an embodiment, in step c) Cyantraniliprole of formula-I is isolated by filtration at a temperature in the range of 0-70oC.

In an embodiment, in step c) filtered Cyantraniliprole of formula-I is washed with solvents selected from water, polar aprotic solvent comprises acetonitrile, dimethylformamide, tetrahydrofuran, ethyl acetate, acetone, dimethylsulfoxide or mixtures thereof; Hydrocarbon solvents such as cyclohexane, hexane, heptane, toluene, xylene or mixtures thereof; or combination or mixtures of solvents, optionally the solvents are used at ambient to at a temperature in the range of 20-70oC.

In an embodiment, in step c) the Cyantraniliprole of formula-I dried at a temperature in the range of 25-100oC.

The process according to the present invention has the following advantages over the known prior art:
• The inorganic base used in the present invention is cost efficient, economical and environment friendly.
• The inorganic base used in the present invention can be separated out easily.
• The process is simple, efficient and environment friendly.
• The process provides Cyantraniliprole with high purity and yield.
• The process of the present invention requires the minimum operations which is economical and efficient on commercial scale.
• Process is carried out in presence of an inorganic base in a selected solvent thus significantly reduces the effluent load.

The following examples are provided to illustrate the invention and are merely for illustrative purpose only and should not be construed to limit the scope of the invention.

Example-01: Preparation of Cyantraniliprole of formula-I.
Charge 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid (100g, 0.33moles), Toluene (300ml), Thionyl Chloride (47.2g, 0.396mole) and DMF (1g) into the reactor and heat the reaction to 70-80°C, continued heating for about 3-5 hour for the completion of reaction, distilled out solvent under vacuum and added ethylene dichloride (100ml). In another reactor charge 2-amino-5-cyano-N, 3-dimethylbenzamide (62.5g, 0.33mole), ethylene dichloride (200ml), sodium carbonate (87.45g, 0.825mole) and water (50ml), add above acid chloride reaction mass dropwise. Stirred the reaction mass for 1-3 hour at 20-25°C, heated further to 45-60°C till completion of reaction, monitor the reaction by HPLC for the formation of cyantraniliprole. The obtained cyantraniliprole was filtered and washed with acetone followed by water. The resulting cyantraniliprole was dried to afford cyantraniliprole of > 95% Purity (by HPLC) with 82% Yield. The obtained product is characterized by 1H NMR: (DMSO-D6, 400MHz) d 2.214 (s, 3H), 2.667-2.679 (d, 3H), 7.423 (s,1H), 7.593-7.625 (q, 1H), 7.764-7.767 (d, 1H), 7.876-7.879 (d, 1H), 8.159-8.183 (dd, 1H), 8.376-8.388 (q, 1H), 8.491-8.507 (dd, 1H), 10.537 (s, 1H)

Example-02: Preparation of Cyantraniliprole of formula-I.
Charge 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid (100g, 0.33moles), dichloromethane (300ml) and Thionyl Chloride (47.2g, 0.396mole) into the reactor and heat the reaction to 30-45°C, continued heating for about 3-5 hour for the completion of reaction, distilled out solvent under vacuum and added ethylene dichloride (100ml). In another reactor charge 2-amino-5-cyano-N, 3-dimethylbenzamide (62.5g, 0.33mole), ethylene dichloride (200ml), sodium carbonate (87.45g, 0.825mole) and water (50ml), add above acid chloride reaction mass dropwise. Stirred the reaction mass for 1-3 hour at 20-25°C, heated further to 45-60°C till completion of reaction, monitor the reaction by HPLC for the formation of cyantraniliprole. The obtained cyantraniliprole was filtered and washed with acetone followed by water. The resulting cyantraniliprole was dried to afford cyantraniliprole of > 95% Purity (by HPLC) with 83.95% Yield.

Example-03: Preparation of Cyantraniliprole of formula-I.
Charge 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid (100g, 0.33moles), Toluene (300ml) and Thionyl Chloride (47.2g, 0.396mole) into the reactor and heat the reaction to 70-80°C, continued heating for about 3-5 hour for the completion of reaction, distilled out solvent under vacuum and added ethylene dichloride (100ml). In another reactor charge 2-amino-5-cyano-N, 3-dimethylbenzamide (62.5g, 0.33mole), ethylene dichloride (200ml), sodium bicarbonate (69.3g, 0.825mole) and water (50ml), add above acid chloride reaction mass dropwise. Stirred the reaction mass for 1-3 hour at 20-25°C, heated further to 45-60°C till completion of reaction, monitor the reaction by HPLC for the formation of cyantraniliprole. The obtained cyantraniliprole was filtered and washed with acetone followed by water. The resulting cyantraniliprole was dried to afford cyantraniliprole of > 95% Purity (by HPLC) with 80% Yield.

Example-04: Preparation of Cyantraniliprole of formula-I.
Charge 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid (100g, 0.33moles), Toluene (300ml), DMF (1g) and Thionyl Chloride (47.2g, 0.396mole) into the reactor and heat the reaction to 70-80°C, continued heating for about 3-5 hour for the completion of reaction, distilled out solvent under vacuum and added dichloromethane (100ml). In another reactor charge 2-amino-5-cyano-N, 3-dimethylbenzamide (62.5g, 0.33mole), dichloromethane (200ml), sodium bicarbonate (69.3g, 0.825mole) and water (50ml), add above acid chloride reaction mass dropwise. Stirred the reaction mass for 1-3 hour at 20-25°C, heated further to 40-50°C till completion of reaction, monitor the reaction by HPLC for the formation of cyantraniliprole. The obtained cyantraniliprole was filtered and washed with acetone followed by water. The resulting cyantraniliprole was dried to afford cyantraniliprole of > 95% Purity (by HPLC) with 77.7% Yield.

Example-05: Preparation of Cyantraniliprole of formula-I.
Charge 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid (100g, 0.33moles), Toluene (300ml) and Thionyl Chloride (47.2g, 0.396mole) into the reactor and heat the reaction to 70-80°C, continued heating for about 3-5 hour for the completion of reaction, distilled out solvent under vacuum and added ethylene dichloride (100ml). In another reactor charge 2-amino-5-cyano-N, 3-dimethylbenzamide (62.5g, 0.33mole), ethylene dichloride (200ml) and sodium carbonate (87.5g, 0.825mole), add above acid chloride reaction mass dropwise. Stirred the reaction mass for 1-3 hour at 20-25°C, heated further to 45-60°C till completion of reaction, monitor the reaction by HPLC for the formation of cyantraniliprole. The obtained cyantraniliprole was filtered and washed with acetone followed by water. The resulting cyantraniliprole was dried to afford cyantraniliprole of > 95% Purity (by HPLC) with 55% Yield.

Example-06: Preparation of Cyantraniliprole of formula-I.
Charge 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid (100g, 0.33moles), Toluene (300ml) and Thionyl Chloride (47.2g, 0.396mole) into the reactor and heat the reaction to 70-80°C, continued heating for about 3-5 hour for the completion of reaction, distilled out the solvent under vacuum and added ethylene dichloride (100ml). In another reactor charge 2-amino-5-cyano-N, 3-dimethylbenzamide (62.5g, 0.33mole), acetonitrile (200ml), sodium carbonate (87.45g, 0.825mole) and water (50ml), add above acid chloride reaction mass dropwise. Stirred the reaction mass for 1-3 hour at 20-25°C, heated further to 45-60°C, Product formation not observed.
From the foregoing it will be observed that numerous modifications and variations can be effectuated without departing from the true spirit and scope of the novel concepts of the present invention. It is to be understood that no limitations with respect to the specific embodiments illustrated is intended or should be inferred. It should be understood that all such modifications and improvements have been deleted herein for the sake of conciseness and readability but are properly within the scope of the following claims.
,CLAIMS:We Claim:
1. An improved process of preparation of Cyantraniliprole of Formula I,

Formula I
said process comprising the steps of:
a) reacting 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, with a chlorinating agent in a suitable solvent to obtain 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride;
b) reacting the 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride with 2-amino-5-cyano-N, 3-dimethylbenzamide, in presence of an inorganic base in a suitable solvent to obtain Cyantraniliprole of formula-I; and
c) isolating the Cyantraniliprole of formula-I.

2. The process as claimed in claim 1, wherein the chlorinating agent used in step a) is selected from thionyl chloride, Oxalyl chloride, Cyanuric chloride, Phosphorus oxychloride, Phosphorus trichloride, Phosphorus pentachloride.

3. The process as claimed in claim 1, wherein the suitable solvent used in step a) is selected from toluene, acetonitrile, methylene chloride, chloroform, xylene, methyl ethyl ketone, benzene, dioxane, hexane, carbon tetrachloride, tetrahydrofuran, dichloromethane, bromodichloromethane, dibromochloromethane, trichlorofluoromethane, 1,1-dichloroethane, 1,2- dichloroethane (ethylene dichloride), 1,1,1-trichloroethane, 1,12-trichloroethane, 1,1,2,2- tetrachloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethylene, trans-1,2- dichloroethylene, trichloroethylene; hydrocarbon solvents such as cyclohexane, heptane or mixtures thereof.

4. The process as claimed in claim 1, wherein the mole equivalents of chlorinating reagent used in step a) are 1.0 to 2.0, preferably 1.2 to 1.5 and more preferably 1.0 to 1.3 mole equivalents with respect to 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid.

5. The process as claimed in claim 1, wherein in step (a) the reaction is performed from 25°C to 125°C for 1 hour to 12 hours, preferably 40-80°C for 1 hour to 5 hours.

6. The process as claimed in claim 1, wherein the inorganic base used in step b) is selected from sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide, lithium carbonate, magnesium carbonate, magnesium hydroxide, cesium carbonate, calcium carbonate, calcium hydroxide or mixtures thereof, preferably sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate.

7. The process as claimed in claim 1, wherein the suitable solvent used in step b) is organic solvents is selected from polar aprotic solvents acetonitrile, dimethylformamide, tetrahydrofuran, ethyl acetate, acetone, dimethylsulfoxide or mixtures thereof; the chlorinating solvents dichloromethane, chloroform, bromodichloromethane, dibromochloromethane, trichlorofluoromethane, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane (ethylene dichloride), 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, trichloroethylene or mixtures thereof; hydrocarbon solvents cyclohexane, hexane, heptane, toluene, xylene or mixtures thereof.

8. The process as claimed in claim 1, wherein the mole equivalents of 2-amino-5-cyano-N, 3-dimethylbenzamide used in step b) are 0.9 to 1.2 with respect to 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid.

9. The process as claimed in claim 1, wherein the solvent used in step b) is selected from ethylene dichloride or dichloromethane or a mixture of ethylene dichloride + water or dichloromethane + water wherein ratio of ethylene dichloride + water or dichloromethane + water is 15:0.5, preferably is in the range of 4:0.5 and more preferably is in the range of 3:0.5.

10. The process as claimed in claim 1, wherein the mole equivalents of inorganic base used in step b) are 0.4 to 2.5, preferably 1.4 to 2.5 mole equivalents with respect to 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid.

11. The process as claimed in claim 1, wherein in the step b) the reaction is performed from 0°C to 90°C for a time period in the range of 1 hour to 60 hours, preferably 30 to 80°C for 2 hour to 10 hours.

12. The process as claimed in claim 1, wherein in step c) Cyantraniliprole of formula-I is isolated by filtration at a temperature in the range of 0-70oC.

13. The process as claimed in claim 1, wherein in step c) filtered Cyantraniliprole of formula-I is washed with solvents selected from water; polar aprotic solvent acetonitrile, dimethylformamide, tetrahydrofuran, ethyl acetate, acetone, dimethylsulfoxide or mixtures thereof; hydrocarbon solvents cyclohexane, hexane, heptane, toluene, xylene or mixtures thereof; or combination or mixtures of solvents, optionally the solvents are used at a temperature in the range of 20-70oC.