Claims:1. An improved process for the preparation of chlorantraniliprole (I)

wherein L is selected from group consisting of ethyl, isopropyl, isobutyl, n-butyl, n-pentyl, and phenyl.
which comprises;
a) reacting 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) with chloroformate in presence of a base in a suitable solvent to get anhydride of formula (II),
b) optionally isolating anhydride of formula (II),
c) treating with 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV), and
d) isolating chlorantraniliprole (I).

2. A compound of formula (II)

Wherein L is selected from group consisting of ethyl, isopropyl, isobutyl, n-butyl, n-pentyl, and phenyl.

3. 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic (isobutyl carbonic) anhydride compound of formula (IIa).

4. An improved process for the preparation of chlorantraniliprole (I)

Wherein R is selected from the group consisting of ethyl or phenyl.
which comprises;
(a) reacting 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) with chlorophosphate in presence of a base in a solvent to get anhydride of formula (IIb),
(b) treating with 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV), and
(c) isolating chlorantraniliprole (I).

5. An improved process for the preparation of chlorantraniliprole (I)

which comprises;
a) dissolving 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III), 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) in presence of a base in a solvent.
b) adding propanephosphonic acid anhydride (T3P) solution to step a) at room temperature,
c) isolating chlorantraniliprole (I).

6. The process as claimed in claim 1, 4 and 5 wherein the base is selected from group consisting of N-methyl morpholine, 1,4-dimethyl piperazine, N-methyl pyrrolidine, triethylamine, N, N-diisopropylethylamine (DIPEA), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 4-diazabicyclo [2.2.2] octane (DABCO), triethanolamine, hydroxy ethyl morpholine, dimethyl aniline, 1-methylpiperidine, pyridine, and substituted pyridines.

7. The process as claimed in claim 1 and 4 wherein the solvent is selected from group consisting of tetrahydrofuran (THF), 2-methyl tetrahydrofuran (2-MeTHF), N, N-dimethylformamide (DMF), 1,2-dimethoxyethane (DME), dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), acetonitrile, acetone, toluene, xylene, mono chlorobenzene, dichlorobenzene, 1,2-dichloromethane and 1,2-dichloroethane.

8. The process as claimed in claim 5, wherein the solvent is selected from group consisting of ethyl acetate, butyl acetate, methyl acetate, isopropyl acetate, n-butyl acetate, tetrahydrofuran, and 1,2-dimethoxyethane.
, Description:FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of chlorantraniliprole (I). The invention also relates to a novel anhydride intermediate (II), and its use in the preparation of chlorantraniliprole (I).

BACKGROUND OF THE INVENTION
Anthranilamide derivatives are a kind of novel insecticides with high efficacy and safety. Chlorantraniliprole is highly effective against insects, which is commercialized by DuPont, and chemically known as 3-Bromo-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide compound of formula (I).

Formula (I)
PCT Patent Publication WO03/015518 discloses the utility of N-acyl anthranilic acid derivatives such as chlorantraniliprole (I). There are several methods reported for preparing anthranilamide derivatives, for example, the process is as shown in scheme -I below:

Chlorantraniliprole (I) WO03/015519 A1 and Bioorganic & Medicinal Chemistry Letters, 17 (2007), 6274-6279 disclose that 3-bromo-l-(3-chloro-2-pyridyl)-lH-pyrazole-5-carboxylic acid reacts with substituted anthranilic acid in the presence of methane sulfonyl chloride and pyridine as acid binding agent to give the benzoxazinone in 86%-92% yield. Then the product reacts with the methylamine to yield the chlorantraniliprole (I). Calculated by 3-bromo-l-(3-chloro-2-pyridyl)-lH-pyrazole-5- carboxylic acids, the total yield of the two-steps is 58%-65%.

The disadvantageous of the above process are involving two step processes from the two advanced intermediates, and the process involved use of excess amount of expensive reagent methane sulfonyl chloride 3.0 to 5.2 mole equivalents and use of expensive solvent like acetonitrile. Theoretical yield of the final step is only 18.7%.

WO2006/062978A1 discloses that 3-bromo-l-(3-chloro-2-pyridyl)-lH-pyrazole-5- carboxylic acid reacts with substituted aminobenzamide in the presence of methanesulfonyl chloride and 3-picoline as acid binding agent to give chlorantraniliprole (I).

The disadvantageous of the above process is usage of expensive reagent methanesulfonyl chloride and purity of compound is not mentioned.

WO2019/207595A1 discloses that 3-bromo-l-(3-chloro-2-pyridyl)-lH-pyrazole-5- carboxylic acid is reacted with a chlorinating agent in a suitable solvent to obtain 3-bromo- 1 -(3- chloro-2-pyridyl)-7-pyrazolc-5-carboxylic acid chloride, followed by reaction of substituted aminobenzamide produces Chlorantraniliprole (I).

The disadvantageous of the above process is the usage of hazardous chlorinating reagent thionyl chloride and the obtained acid chloride is unstable to purify.

The main objective of the present invention is to provide a simple, economical, commercially and environmentally feasible process for the preparation of chlorantraniliprole (I) with high yield and purity.

SUMMARY OF THE INVENTION
In one aspect of the present invention is to provide an improved process for the preparation of chlorantraniliprole (I).

Wherein L is selected from the group consisting of ethyl, isopropyl, isobutyl, n-butyl, n-pentyl, and phenyl.
which comprises;
(a) reacting 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) with chloroformate in presence of a base in a suitable solvent to get anhydride of formula (II),
(b) optionally isolating anhydride of formula (II),
(c) treating with 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV), and
(d) isolating chlorantraniliprole (I).

In another aspect of the present invention provides a novel anhydride intermediate of formula (II).

Formula (II)
Wherein L is selected from the group consisting of ethyl, isopropyl, isobutyl, n-butyl, n-pentyl, and phenyl.

In yet another aspect of the present invention provides a novel isobutyl anhydride intermediate of formula (IIa).

Formula (IIa)
In yet another aspect of the present invention is to provide an improved process for the preparation of chlorantraniliprole (I).

Wherein R is selected from the group consisting of ethyl or phenyl.
which comprises;
(a) reacting 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) with chlorophosphate in presence of a base in a suitable solvent to get anhydride of formula (IIb),
(b) treating with 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV), and
(c) isolating chlorantraniliprole (I).

In yet another aspect of the present invention is to provide an improved process for the preparation of chlorantraniliprole (I).

which comprises;
a) dissolving 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III), 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) in a solvent in presence a base at room temperature.
b) adding propanephosphonic acid anhydride (T3P) solution to step a) at room temperature, and
c) isolating chlorantraniliprole (I).

In yet another aspect of the present invention is to provide a simple, economical, and commercially feasible process for the synthesis of chlorantraniliprole (I) with high yield and purity.

DETAILED DESCRIPTION OF THE INVENTION
It is to be understood that the description of the present invention has been simplified to illustrate elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that may be well known.

In one embodiment of the present invention is to provide an improved process for the preparation of chlorantraniliprole (I).

Wherein L is selected from the group consisting of ethyl, isopropyl, isobutyl, n-butyl, n-pentyl, and phenyl.
which comprises;
(a) reacting 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) with chloroformate in presence of a base in a suitable solvent to get anhydride of formula (II),
(b) optionally isolating anhydride of formula (II),
(c) treating with 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV), and
(d) isolating chlorantraniliprole (I).

According to the present embodiment, 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) is reacted with chloroformate in presence of a base in a suitable solvent at room temperature for 10-30 min to obtain anhydride compound of formula (IIa). Treating anhydride of formula (IIa) with 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) at a temperature of 40oC to 100oC for 2 to 4 hrs to get the crude product. Methanol is added to the obtained crude product and stirred at 0-5oC for 15-30 min and filtered to get chlorantraniliprole (I).

According to the present embodiment, the solvent used in the reaction is selected from group consisting of polar-aprotic solvents such as tetrahydrofuran (THF), 2-methyl tetrahydrofuran (2-MeTHF), N, N-dimethylformamide (DMF), 1,2-dimethoxyethane (DME), dimethylacetamide (DMAc) and dimethyl sulfoxide (DMSO); nitrile solvents such as acetonitrile, propionitrile and butyronitrile; ketone solvents such as acetone, methyl ethyl ketone and methyl isobutyl ketone; hydrocarbon solvents such as toluene, xylene, mono chlorobenzene, and dichlorobenzene; chlorinated solvents such as 1,2-dichloromethane and 1,2-dichloroethane. Preferably tetrahydrofuron.

According to the present embodiment, the base used in the reaction is selected from group consisting of N-methyl morpholine, N-methyl piperidine, 1,4-dimethyl piperazine, N-methyl pyrrolidine, triethylamine, N, N-diisopropylethylamine (DIPEA), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 4-diazabicyclo [2.2.2] octane (DABCO), triethanolamine, hydroxy ethyl morpholine, dimethyl aniline, pyridine, and substituted pyridines. Preferably N-methyl morpholine.

In another embodiment of the present invention provides a novel anhydride intermediate of formula (II).

Formula (II)
Wherein L is selected from the group consisting of ethyl, isopropyl, isobutyl, n-butyl, n-pentyl, and phenyl.

In another embodiment of the present invention is to provide a novel isobutyl anhydride intermediate of Formula (IIa).

Formula (IIa)
Chemical Name: 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic (isobutyl carbonic) anhydride.
Characterized by 1H NMR (400 MHZ, CDCl3) δ 8.50 (dd, 1H, J = 1.63 HZ, 4.70 HZ), 7.90 (dd, 1H, J = 1.63 HZ, 8.0 HZ), 7.43 (dd, 1H, J = 4.71 HZ, 8.0 HZ), 7.03 (s, 1H), 3.95 (d, 2H, J = 6.75 HZ), 1.90-1.80 (m, 1H), 0.85 (d, 6H, J = 6.0 HZ).

In yet another embodiment of the present invention is to provide an improved process for the preparation of chlorantraniliprole (I).

Wherein R is selected from the group consisting of ethyl or phenyl.
which comprises;
(a) reacting 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) with chlorophosphate in presence of a base in a suitable solvent to get anhydride of formula (IIb),
(b) treating with 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV), and
(c) isolating chlorantraniliprole (I).

According to the present embodiment, the chlorophosphate is selected from the group consisting of diethyl chlorophosphate or diphenyl chlorophosphate.

According to the present embodiment, the solvent used in the reaction is selected from group consisting of polar-aprotic solvents such as tetrahydrofuran (THF), 2-methyl tetrahydrofuran (2-MeTHF), N, N-dimethylformamide (DMF), 1,2-dimethoxyethane (DME), dimethylacetamide (DMAc) and dimethyl sulfoxide (DMSO); nitrile solvents such as acetonitrile, propionitrile and butyronitrile; ketone solvents such as acetone, methyl ethyl ketone and methyl isobutyl ketone; hydrocarbon solvents such as toluene, xylene, mono chlorobenzene, and dichlorobenzene; chlorinated solvents such as 1,2-dichloromethane and 1,2-dichloroethane. Preferably tetrahydrofuran.

According to the present embodiment, the base used in the reaction is selected from group consisting of N-methyl morpholine, N-methyl piperidine, 1,4-dimethyl piperazine, N-methyl pyrrolidine, pyridine and triethylamine. Preferably N-methyl morpholine.

In yet another embodiment of the present invention is to provide an improved process for the preparation of chlorantraniliprole (I).

which comprises;
a) dissolving 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III), 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) in a solvent in presence a base at room temperature.
b) adding propanephosphonic acid anhydride (T3P) solution to step a) at room temperature,
c) isolating chlorantraniliprole (I).

According to the present embodiment, the solvent used in the reaction is selected from group consisting of ester solvents such as ethyl acetate, methyl acetate, isopropyl acetate, and n-butyl acetate; polar-aprotic solvents such as tetrahydrofuran (THF), 2-methyl tetrahydrofuran (2-MeTHF), and 1,2-dimethoxyethane (DME). Preferably ethyl acetate.

According to the present embodiment, the base used in the reaction is selected from group consisting of N-methyl morpholine, N-methyl piperidine, 1,4-dimethyl piperazine, N-methyl pyrrolidine, triethylamine, pyridine and substituted pyridines. Preferably N-methyl morpholine.

According to the present embodiment 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid compound of Formula (III) is prepared as per the procedure described in WO2003016283A1.

According to the present embodiment 2-amino-5-chloro-N,3-dimethylbenzamide compound of Formula (IV) is prepared as per the procedure described in WO2003015519A1 and WO2006062978A1.

According to the present embodiment, process for the preparation of chlorantraniliprole (I) provides a simple, economical, and commercially feasible with high yield and purity.

 
The advantage of the invention:
1. One pot synthesis
2. Mild reaction conditions with less operations
3. Use of inexpensive economically viable reagents
4. Involves simple filtration method and zero effluents
5. No further purification required
6. All solvents recovered and reused
Comparison of experimental data with various leaving groups.
Leaving group Yield Purity Process feasibility
Acid chloride 85% >97% • Involves more hazardous reagents
• Involves higher temperature
• Unstable intermediates
• This process is not cost effective
Anhydride 85% >98% • Less hazardous
• Reaction completes at lower temperature
• Anhydride intermediate is stable and filterable to get pure compound
• Cost effective in comparison of acid chloride process
Phosphate 90% 99% • Less hazardous
• Reaction completes at lower temperature
• Anhydride intermediate is stable and filterable to get pure compound
• Cost effective in comparison of acid chloride process

The further embodiment of the present invention is illustrated by the following examples, which are provided merely to be exemplary of the inventions and is not intended to limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

EXAMPLES
Example 1: Preparation of isobutyl anhydride intermediate (IIa)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (2.0 gm, 1.0 eq) and THF (10 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (0.668 gm, 1.0 eq) and isobutyl chloroformate (0.903 gm, 1.0 eq) and stirred at RT for 15 minutes. After completion of reaction, remove the solvent under reduced pressure to get isobutyl anhydride intermediate (IIa).
1H NMR (400 MHZ, CDCl3) δ 8.50 (dd, 1H, J = 1.63 HZ, 4.70 HZ), 7.90 (dd, 1H, J = 1.63 HZ, 8.0 HZ), 7.43 (dd, 1H, J = 4.71 HZ, 8.0 HZ), 7.03 (s, 1H), 3.95 (d, 2H, J = 6.75 HZ), 1.90-1.80 (m, 1H), 0.85 (d, 6H, J = 6.0 HZ).
Example 2: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (2.0 gm, 1.0 eq) and THF (10 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (0.668 gm, 1.0 eq) and isobutyl chloroformate (0.903 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (1.313 gm, 1.0 eq) was dissolved in THF and added to Reaction mixture at 60-65oC and stirred at reflux for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 99% purity.
Example 3: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (5.0 gm, 1.0 eq) and Toluene (50 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-Methyl morpholine (1.672 gm, 1.0 eq) and isopropyl chloroformate (1.924 gm, 0.95 eq) and stirred at RT for 15 minutes Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (3.282 gm, 1.0 eq) was dissolved in Toluene and added to reaction mixture at 60-65oC and stirred at 80 oC for 2-2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 98% purity.
Example 4: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (2.0 gm, 1.0 eq) and THF (10 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge 1,4-dimethylpiperazine (0.755 gm, 1.0 eq) and isobutyl chloroformate (0.858 gm, 0.95 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (1.313 gm, 1.0 eq) was dissolved in THF and added to Reaction mixture at 60-65oC and stirred at reflux for 2-2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 98.90% purity.

Example 5: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (2.0 gm, 1.0 eq) and THF in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methylpyrrolidine (0.563 gm, 1.0 eq) and isobutyl chloroformate (0.903 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (1.313 gm, 1.0 eq) was dissolved in THF and added to Reaction mixture at 60-65 oC and stirred at reflux for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 99.70% purity.
Example 6: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (5.0 gm, 1.0 eq) and Toluene (50 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (1.672 gm, 1.0 eq) and isobutyl chloroformate (2.144 gm, 0.95 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (3.282 gm, 1.0 eq) was dissolved in Toluene and added to Reaction mixture at 60-65oC and stirred at 80oC for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 98% purity.
Example 7: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (2.0 gm, 1.0 eq) and EDC (10 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-Methyl morpholine (0.668 gm, 1.0 eq) and isobutyl chloroformate (0.903 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (1.313 gm, 1.0 eq) was dissolved in EDC and added to Reaction mixture at 60-65oC and stirred at 60-65oC for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 98% purity.
Example 8: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (5.0 gm, 1.0 eq) and Toluene (50 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (1.671 gm, 1.0 eq) and Ethyl chloroformate (1.704 gm, 0.95 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (3.118 gm, 0.95 eq) was dissolved in Toluene and added to Reaction mixture at 60-65 oC and stirred at 80 oC for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 95.45% purity.
Example 9: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (0.5 gm, 1.0 eq) and THF (8 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (0.167 gm, 1.0 eq) and phenyl chloroformate (0.258 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (0.328 gm, 1.0 eq) was dissolved in THF and added to Reaction mixture at 60-65 oC and stirred at reflux for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 98% purity.
Example 10: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (0.5 gm, 1.0 eq) and THF (8 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (0.167 gm, 1.0 eq) and n-pentyl chloroformate (0.249 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (0.328 gm, 1.0 eq) was dissolved in THF and added to Reaction mixture at 60-65 oC and stirred at reflux for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 97% purity.
Example 11: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (0.5 gm, 1.0 eq) and THF (8 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (0.167 gm, 1.0 eq) and n-butyl chloroformate (0.225 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (0.328 gm, 1.0 eq) was dissolved in THF and added to Reaction mixture at 60-65 oC and stirred at reflux for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 80-85% yield and 98% purity.
Example 12: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (5.0 gm, 1.0 eq) and Toluene (50 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (1.671 gm, 1.0 eq) and diethyl chlorophosphate (2.851 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (3.118 gm, 0.95 eq) was dissolved in toluene and added to Reaction mixture at 60-65 oC and stirred at 80 oC for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 75-80% yield and 99% purity.
Example 13: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (1.0 gm, 1.0 eq) and THF (10 mL) in a three neck RBF equipped with chilled water condenser and thermometer pocket. Charge N-methyl morpholine (0.451 gm, 1.0 eq) and diphenyl chlorophosphate (0.888 gm, 1.0 eq) and stirred at RT for 15 minutes. Then 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (0.656 gm, 1.0 eq) was dissolved in THF and added to Reaction mixture at 60-65 oC and stirred at reflux oC for 2 – 2.5 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get Chlorantraniliprole (I) with 75-80% yield and 99% purity.
Example 14: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (10.0 gm, 1.0 eq), 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (6.565 gm, 1.0 eq), pyridine (10 mL, 1 Vol) and ethyl acetate (20 mL, 2 Vol) in a three neck RBF equipped with chilled water condenser and thermometer pocket at room temperature. Then propanephosphonic acid anhydride (T3P, 50% solution in ethyl acetate) (21.036 g, 2.0 eq) was added to reaction mixture in dropwise mode at room temperature and stirred at RT for 18-20 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 85-90% yield and 99% purity.

Example 15: Preparation of chlorantraniprole (I)
Charge 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid of formula (III) (10.0 gm, 1.0 eq), 2-amino-5-chloro-N,3-dimethylbenzamide of formula (IV) (6.565 gm, 1.0 eq), N-methyl morpholine (6.687, 2.0 eq) and ethyl acetate (25 mL, 2.5 Vol) in a three neck RBF equipped with chilled water condenser and thermometer pocket at room temperature. Then propanephosphonic acid anhydride (T3P, 50% solution in ethyl acetate) (21.036 g, 2.0 eq) was added to reaction mixture in dropwise mode at room temperature and stirred at RT for 18-20 h. After completion of reaction, remove the solvent under reduced pressure. Methanol was added to the obtained crude product and stirred at 0-5oC for 15-30 minutes and filtered to get chlorantraniliprole (I) with 85-90% yield and 99% purity.