WO2023073502A1 - Procédés de préparation de composés intermédiaires de pyrazole-carboxylate et d'anthranilamide - Google Patents

Procédés de préparation de composés intermédiaires de pyrazole-carboxylate et d'anthranilamide Download PDF

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WO2023073502A1
WO2023073502A1 PCT/IB2022/059981 IB2022059981W WO2023073502A1 WO 2023073502 A1 WO2023073502 A1 WO 2023073502A1 IB 2022059981 W IB2022059981 W IB 2022059981W WO 2023073502 A1 WO2023073502 A1 WO 2023073502A1
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formula
compound
solvent
methyl
oxidizing agent
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PCT/IB2022/059981
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Srinivas Simhadri
Nagaraju MEKALA
Srinivasa Rao BUDDEPU
Karunakara Rao Javvaji
Chiranjeevi CHEEKATI
Durgaprasad Kuchipudi
Uma Maheswer Rao VASIREDDI
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Laurus Labs Limited
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Publication of WO2023073502A1 publication Critical patent/WO2023073502A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to methods for preparation of 2-amino-5-chloro-N-3- dimethylbenzamide compound of Formula IV and pyrazole-carboxylate compound of Formula VI, an intermediates useful for preparation of certain anthranilamide compounds, for example chlorantraniliprole and/or cyantraniliprole.
  • Chlorantraniliprole and Cyantraniliprole chemically known as 3-Bromo-N-[4-chloro-2-methyl-6-(methyl carbamoyl) phenyl] -l-(3-chloro- 2- pyridine-2-yl)- lH-pyrazole-5-carboxamide and 3-bromo- l-(3-chloro-2-pyridyl)-4- cyano-2-methyl-(methyl carbamoyl) pyrazole-5-carboxanilide respectively and are having the following chemical structures: Chlorantraniliprole and Cyantraniliprole are a new 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 lsoptera species.
  • PCT application Number: 2003/015518 discloses a process for preparation of pyrazole-carboxylate intermediate, specifically Ethyl 3-bromo-l-(3- chloro-2-pyridinyl)-lh-pyrazole-5-carboxylate through an oxidation of Ethyl 3-bromo-l -(3-chloro-2-pyridinyl)-4,5-dihydro- lH-pyrazole-5-carboxylate.
  • the disclosed oxidation process involves addition of starting material, potassium persulfate, sulfuric acid in acetonitrile followed by heating to reflux for the reaction completion.
  • the process disclosed in the ‘518 publication is as follows:
  • Zhengming Li et al in Journal of Agricultural and Food Chemistry 2020, 68, 40, 11282-11289 discloses a process for preparation of Ethyl 3-bromo-l-(3-chloro-2- pyridinyl)-lh-pyrazole-5-carboxylate through an oxidation of Ethyl 3-bromo-l-(3- chloro-2-pyridinyl)-4,5-dihydro-lH-pyrazole-5-carboxylate in acetonitrile in the presence of potassium persulfate using sulfuric acid as a catalyst at 75°C.
  • the process disclosed by Zhengming Li et al. is as follows:
  • Anthranilamide compounds such as chlorantramliprole and cyantraniliprole are the important insecticides available in the market. 2-amino-5-chloro-N-3- dimethylbenzamide and pyrazole-carboxylate intermediates are the key cost contributors in the preparation of these anthranilamide compounds.
  • the key step in the preparation of pyrazole-carboxylate intermediate is the use of oxidizing agent for example potassium persulfate in the oxidation reaction.
  • oxidizing agent for example potassium persulfate
  • potassium persulfate is possibly undergo thermal decomposition and releases oxygen gas as well as noxious fog or fumes of sulfur dioxide and this leading to incomplete conversion of starting materials and getting low product yield.
  • the compound of Formula IV and pyrazole-carboxylate compound of Formula VI are the key cost contributors in the preparation of anthranilamide compounds. Hence, it is always desired to improve the product yield, quality of its intermediates involved in the preparation of these anthranilamide compounds and there by reducing the manufacturing cost.
  • the main object of the present invention is to provide a simple, cost effective, high yield process for the preparation of intermediate compound of Formula IV and pyrazole-carboxylate compound of Formula VI with avoiding the aforementioned problems. Further, the present invention relates to conversion of the compound of Formula IV and/or pyrazole-carboxylate of Formula VI intermediates in to certain anthranilamide compounds, such as for example chlorantraniliprole or cyantraniliprole.
  • the present invention provides an improved process for preparation of compound of Formula IV and pyrazole-carboxylate of Formula VI intermediates. Further, the present invention provides an improved process for preparation of certain anthranilamide compounds for example, chlorantraniliprole and/or cyantraniliprole through preparing the compound of Formula IV and/or compound of Formula VI intermediates of the present invention.
  • the present invention provides an improved process for preparation of compound of Formula IV, comprising:
  • the present invention provides an improved process for preparation of compound of Formula IV, comprising: a) reacting a compound of Formula I with a source of chloride in a suitable solvent to obtain a compound of Formula II, b) reacting the compound of Formula II with phosgene or its derivative and a suitable base to obtain a compound of Formula III, and c) reacting the compound of Formula III with a source of monomethyl amine to obtain a compound of Formula IV; wherein the steps a) to c) are carried out in one-pot reaction.
  • the present invention provides an improved process for preparation of compound of Formula IV, comprising: a) reacting a compound of Formula I with a source of chloride in a suitable solvent to obtain a compound of Formula II, b) reacting the compound of Formula II with phosgene or its derivative and a suitable base to obtain a compound of Formula III, and c) reacting the compound of Formula III with a source of monomethyl amine to obtain a compound of Formula IV; wherein the steps b) and c) are carried out in one-pot reaction.
  • the present invention provides an improved process for preparation of compound of Formula IV, comprising: a) reacting a compound of Formula I with a source of chloride in a suitable solvent to obtain a compound of Formula II, b) reacting the compound of Formula II with phosgene or its derivative and a suitable base to obtain a compound of Formula III, c) reacting the compound of Formula III with a source of monomethyl amine to obtain a compound of Formula IV, d) adding water to the step c) reaction mass, e) optionally, concentrating the solution at below 50°C, f) optionally, adding an organic solvent to the step e) reaction mass, and g) filtering the compound of Formula IV.
  • the present invention provides an improved process for preparation of compound of Formula IV, comprising: a) reacting a compound of Formula I with a source of chloride in a suitable solvent to obtain a compound of Formula II, b) adding water and a suitable base to the step a) reaction mass, c) optionally, concentrating the solution at below 50°C, d) filtering the compound of Formula II, e) reacting the compound of Formula II with phosgene or its derivative and a suitable base to obtain a compound of Formula III, and f) reacting the compound of Formula III with a source of monomethyl amine to obtain a compound of Formula IV.
  • the present invention provides an improved process for preparation of compound of Formula IV, comprising: a) reacting a compound of Formula I with a source of chloride in a suitable solvent to obtain a compound of Formula II, b) adding water and a suitable base to the step a) reaction mass, c) optionally, concentrating the solution at below 50°C, d) filtering the compound of Formula II, e) reacting the compound of Formula II with phosgene or its derivative and a suitable base in a suitable solvent to obtain a reaction solution of compound of Formula III, f) reacting the solution of compound of Formula III of step e) with a source of monomethyl amine, g) adding water to the step f) reaction mass, h) optionally, concentrating the solution at below 50°C, i) optionally, adding an organic solvent to the step h) reaction mass, and j) isolating the compound of Formula IV.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: reacting a compound of Formula V with a suitable oxidizing agent, an acid in a suitable organic solvent to obtain a compound of Formula VI; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl and wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: reacting a compound of Formula V with a suitable oxidizing agent, an acid in a suitable organic solvent to obtain a compound of Formula VI; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity and wherein the each part contains about 0.1 to about 0.5 equivalents of oxidizing agent to the starting compound of Formula V.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: reacting a compound of Formula V with a suitable oxidizing agent, an acid in a suitable organic solvent to obtain a compound of Formula VI; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity at a temperature of about 0°C to about 60°C and wherein the each part contains about 0.1 to about 0.5 equivalents of oxidizing agent to the starting compound of Formula V.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising:
  • Rl is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and C alkyl; a) dissolving a compound of Formula V in a suitable organic solvent, b) adding an acid to the step a) solution, c) adding first part of suitable oxidizing agent at a temperature of about 0°C to about 60°C, d) heating the solution to about 65°C to reflux, e) cooling the solution to about 0°C to about 60°C, f) adding second part of suitable oxidizing agent at a temperature of about 0°C to about 60°C, g) repeating the steps d) to f) until complete addition of the remaining parts of suitable oxidizing agent, and h) isolating the compound of Formula VI; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: a) dissolving a compound of Formula V in a suitable organic solvent, b) adding an acid to the step a) solution, c) adding first part of suitable oxidizing agent at a temperature of about 0°C to about 60°C, d) heating the solution to about 65°C to reflux, e) cooling the solution to about 0°C to about 60°C, f) adding second part of suitable oxidizing agent at a temperature of about 0°C to about 60°C, g) repeating the steps d) to f) until complete addition of the remaining parts of suitable oxidizing agent, and h) isolating the compound of Formula VI; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and C alkyl; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity; and wherein the each part
  • the present invention provides an improved process for preparation of compound of Formula VI, wherein the Rl” is methyl or ethyl, wherein the R2, R5-R7 are each hydrogen, wherein the R3 is bromo and wherein the R4 is chloro.
  • the present invention provides a process for preparation of compound of Formula VI having N-oxide impurity less than 0.5% by HPLC, comprising: a) dissolving a compound of Formula VI having about 0.5% or more N-oxide impurity by HPLC in a suitable solvent, b) adding an anti- solvent to the step a) solution, and c) Isolating the compound of Formula VI having N-oxide impurity less than 0.5% by HPLC; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2- R7 is independently selected from hydrogen, halogen and CM alkyl.
  • the present invention provides a process for preparation of compound of Formula VI having N-oxide impurity less than 0.5% by HPLC, comprising: a) dissolving a compound of Formula VI having about 0.5% or more N-oxide impurity by HPLC in a suitable solvent, b) adding an anti- solvent to the step a) solution, and c) isolating the compound of Formula VI having N-oxide impurity less than 0.5% by HPLC; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl; wherein the suitable solvent is selected from the group comprising amides, esters, ketones, nitriles, halogenated hydrocarbons, aromatic hydrocarbons and mixtures thereof; the anti- solvent is selected from the group comprising ethers, aliphatic and alicyclic hydrocarbon, water and mixture thereof.
  • the present invention provides an improved process for preparation of chlorantraniliprole , comprising:
  • Chlorantraniliprole a) preparing a compound of Formula IV and/or compound of Formula VI according to the processes described as above embodiments, and b) converting the compound of Formula IV and/or compound of Formula VI in to chlorantraniliprole; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl.
  • the present invention provides an improved process for preparation of cyantraniliprole, comprising: a) preparing a compound of Formula VI according to processes described as above embodiments, and b) converting the compound of Formula VI in to cyantraniliprole; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl.
  • the present invention provides a composition comprising chlorantraniliprole or cyantraniliprole, prepared by the process of compound of Formula IV and /or compound of Formula VI of the present invention and/or at least one excipient.
  • the present invention encompasses improved processes for the preparation of compound of Formula IV and compound of Formula VI with high product yield and quality.
  • the present invention encompasses an improved process for the preparation of compound of Formula IV with high product yield and quality, wherein the improvements involve use of one -pot process without isolating intermediate compounds in a single solvent system and avoids multiple solvent systems and cumbersome isolations such as time consuming solvent workups, drying and necessity of analyzing the compounds at each stage.
  • the present invention provides an improved process for preparation of compound of Formula IV, comprising:
  • the present invention provides an improved process for preparation of compound of Formula IV, wherein the steps a) to c) are carried out in one-pot reaction and without isolating the intermediates II and III as solid.
  • the present invention provides an improved process for preparation of compound of Formula IV, wherein the steps b) and c) are carried out in one-pot reaction and without isolating the intermediate III as solid.
  • one -pot as used in this application means a process uses a strategy to improve the efficiency of a chemical reaction whereby a reactant is subjected to successive chemical reactions in just one solvent/reactor. This is much desired by chemists because avoiding a lengthy separation process and purification of the intermediate chemical compounds can save time and resources, improves the efficiency of a chemical reaction, and offers better chemical yield.
  • compositions comprising, “comprising,” “consist,” “consisting,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion.
  • a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.
  • the source of chloride used for reacting a compound of Formula I in aforementioned step a) is selected from the group comprising but not limited to but not limited to sulfuryl chloride, N-chlorosuccinimide, chlorine gas, metal chloridc-FTCF in acid aqueous medium, HCI-H2O2, m-chloroperbenzoic acid/HCl, acetyl chloride and the like; preferably Sulfuryl chloride or N-Chlorosuccinimide; more preferably Sulfuryl chloride.
  • the suitable solvent used for reacting a compound of Formula I with a source of chloride in aforementioned step a) is selected from the group comprising but not limited to amides, esters, ketones, nitriles, ethers, halogenated hydrocarbons, aromatic hydrocarbons and the like and mixtures thereof.
  • the amides include, but are not limited to dimethylacetamide, dimethylformamide, N-methylpyrrolidone and the like; esters include, but are not limited to ethyl acetate, methyl acetate and the like; ketones include, but are not limited to acetone, methyl isobutyl ketone, methyl ethyl ketone and the like; nitriles include, but are not limited to acetonitrile, propionitrile and the like; ethers include, but are not limited to tetrahydrofuran, methyl tetrahydrofuran, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like; halogenated hydrocarbons include, but are not limited to methylene chloride, ethylene chloride, chloroform and the like; aromatic hydrocarbons include, but are not limited to toluene, xylene and the like and mixture
  • the reaction of a Formula I with a source of source of chloride is carried out at a temperature of about 25 °C to reflux temperature; preferably at about 25°C to about 45°C; more preferably at about 25°C to about 35°C.
  • step a) solution advantageously processed to next step by adding a phosgene or its derivative and a suitable base in a suitable solvent to the step a) solution without isolating the compound of Formula II as solid.
  • the resultant compound of formula II may be isolated as a solid by conventional techniques and processed for further stages.
  • the resultant compound of formula II may be isolated as a solid by adding water to the reaction mass and followed by adjusting pH of the reaction mass to above 7 with a suitable base, optionally concentrating the reaction mass under vacuum at below 50°C. Then the compound of Formula II can be isolated from reaction mass by conventional techniques such as solvent extraction, solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration; preferably by filtering the solids.
  • the phosgene or its derivative as used in the aforementioned step b) is selected from phosgene as in gaseous form or as in liquid form comprising but not limited to phosgene, diphosgene, triphosgene, bromophosgene and the like; preferably triphosgene.
  • the suitable base used for reacting the compound of Formula II with phosgene or its derivative in aforementioned step b) is selected from the group comprising but not limited to inorganic bases selected from alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and the like; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert- butoxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate and the like; alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate and the like; organic bases selected from the group comprising triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropyl ethylamine, N-methyl morpholine, piperidine, 2-picoline, 3-picoline and the like and mixtures thereof; preferably an inorganic base such as sodium carbonate
  • the step b) is carried out in presence of a suitable second solvent.
  • the suitable second solvent used in aforementioned step b) is selected from the group comprising but not limited to amides, esters, ketones, nitriles, ethers, halogenated hydrocarbons, aromatic hydrocarbons and the like and mixtures thereof.
  • the amides include, but are not limited to dimethylacetamide, dimethylformamide, N- methylpyrrolidone and the like; esters include, but are not limited to ethyl acetate, methyl acetate and the like; ketones include, but are not limited to acetone, methyl isobutyl ketone, methyl ethyl ketone and the like; nitriles include, but are not limited to acetonitrile, propionitrile and the like; ethers include, but are not limited to tetrahydrofuran, methyl tetrahydrofuran, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like; halogenated hydrocarbons include, but are not limited to methylene chloride, ethylene chloride, chloroform and the like; aromatic hydrocarbons include, but are not limited to toluene, xylene and the like and
  • the suitable second solvent used in aforementioned step b) is same as the solvent used in step a) of the aforesaid process; preferably ethyl acetate, acetonitrile or methylene chloride; more preferably methylene chloride.
  • the reaction of Formula II with phosgene or its derivative is carried out at a temperature of about 0°C to reflux temperature; preferably at about 25°C to about 40°C.
  • step b) solution advantageously processed to next step by adding a source of monomethylamine to the step b) solution without isolating the compound of Formula III as a solid.
  • the source of monomethylamine used in aforementioned step c) is selected from the group comprising but not limited to aqueous methyl amine, methyl amine in solvent, methyl amine gas and the like; preferably aqueous methyl amine or methyl amine gas.
  • reaction of compound of Formula III with a source of monomethyl amine is carried out in presence of a suitable acid or a suitable base.
  • the suitable acid optionally used in aforementioned step c) is selected from the group comprising but not limited to acetic acid, formic acid, methanoic acid and the like.
  • the suitable base optionally used in aforementioned step c) is selected from the group comprising but not limited to inorganic bases selected from alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and the like; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert- butoxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate and the like; alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate and the like; organic bases selected from the group comprising but not limited to triethylamine, isopropyl ethylamine, diisopropyl amine, diisopropyl ethylamine, N-methyl morpholine, piperidine, pyridine, 2-picoline, 3- picoline and the like and mixtures thereof.
  • inorganic bases selected from alkali metal hydroxides such as lithium hydro
  • the reaction of a Formula III with a source of monomethylamine is carried out at a temperature of about 25 °C to reflux temperature; preferably at about 25°C to about 45°C more preferably at about 25°C to about 35°C.
  • the present invention provides an improved process for the preparation of chlorantraniliprole or a salt thereof, comprising preparing the compound of Formula IV as process described above, and converting the compound of Formula IV in to chlorantraniliprole or a salt thereof by any process known in the art for example W02006/062978 or by the process described in the present specification.
  • the present invention encompasses an improved process for the preparation of pyrazole-carboxylate intermediate with high product yield and quality, wherein the improvements involve part wise and predefined quantity of addition of oxidizing agent at lower temperature to avoid decomposition of oxidizing agent and thereby attaining complete conversion of starting material.
  • the present invention further relates to a process for purification of pyrazole- carboxylate intermediate which is substantially free of N-oxide impurity.
  • the pyrazole-carboxylate intermediate is one of the key cost contributor in the preparation of certain anthranilamide compounds, for example chlorantraniliprole and cyantraniliprole.
  • Oxidation process according to the process disclosed in the art involves either adding entire potassium persulfate at higher temperature (at 75°C) in one part in to the reaction mass or in two parts. Generally at higher temperature (70-75°C) potassium persulfate is having tendency to thermal decomposition and thereby releases excess oxygen also emit noxious fog or fumes of Sulfur dioxide (SO2), Peroxydisulfate (S2O8) and Potassium oxide (K 2 O) and thereby chances of ignition due to excess oxygen levels.
  • SO2 sulfur dioxide
  • S2O8 Peroxydisulfate
  • K 2 O Potassium oxide
  • the present invention provides process to oxidize compound of Formula V completely by avoiding decomposition of potassium persulfate. Further, it is also important to minimize the N-oxide impurity in compound of Formula VI.
  • the present invention provides an improved process for oxidation of Formula V, which involves part wise addition of oxidizing agent (about 3 to about 10 parts) and predefined quantity (about 0.1 to 0.5 equivalents of oxidizing agent to the starting compound of Formula V) of oxidizing agent for each part at lower temperature to avoid decomposition of oxidizing agent and thereby attaining complete conversion of starting material. Further, the present invention also provides effective purification process of Formula VI to minimize the N-oxide impurity.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: reacting a compound of Formula V with a suitable oxidizing agent, an acid in a suitable organic solvent to obtain a compound of Formula VI; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl; and wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity.
  • CM alkyl used herein is selected from but not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, /c/7-butyl and the like.
  • a suitable substituent which may be selected from the group comprising halogen, aryl and the like.
  • halogen used herein is selected from bromo, chloro and Iodo.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: reacting a compound of Formula V with a suitable oxidizing agent, an acid in a suitable organic solvent to obtain a compound of Formula VI; wherein the “Rl” is selected from hydrogen or CH alkyl; preferably methyl or ethyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl, preferably R2 and R5-R7 are hydrogen, R3 is bromo and R4 is chloro; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity and wherein the each part contains about 0.1 to about 0.5 equivalents of oxidizing agent to the starting compound of Formula V.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: reacting a compound of Formula V with a suitable oxidizing agent, an acid in a suitable organic solvent to obtain a compound of Formula VI; oxidizing agent, an acid in a suitable organic solvent to obtain a compound of Formula VI; wherein the “Rl” is selected from hydrogen or C alkyl, preferably methyl or ethyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl, preferably R2 and R5-R7 are hydrogen, R3 is bromo and R4 is chloro; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity and wherein the each part contains about 0.1 to about 0.5 equivalents of oxidizing agent to the starting compound of Formula V, at a temperature of about 0°C to about 60°C.
  • the present invention provides an improved process for preparation of compound of Formula VI, comprising: a) dissolving a compound of Formula V in a suitable organic solvent, b) adding an acid to the step a) solution, c) adding first part of suitable oxidizing agent at a temperature of about 0°C to about 60°C, d) heating the solution to about 65°C to reflux, e) cooling the solution to about 0°C to about 60°C, f) adding second part of suitable oxidizing agent at a temperature of about 0°C to about 60°C, g) repeating the steps d) to f) until complete the addition of the remaining parts of suitable oxidizing agent, and h) isolating the compound of Formula VI; wherein the “Rl” is selected from hydrogen or CM alkyl, preferably methyl or ethyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl, preferably R2 and R5-R7 are hydrogen,
  • the compound of Formula Va which is used herein as a starting material is known in the art and can be prepared by any known methods. For example, may be prepared as per the process disclosed in W02003/015519.
  • the suitable oxidizing agent used in aforementioned process is selected from the group comprising but not limited to bromine, hydrogen peroxide (H2O2), Potassium persulfate (K2S2O8), sodium persulfate (Na2S20s), ammonium persulfate ((NFU)2S2O8), potassium monopersulfate (KHSO5), sodium monopersulfate (NaHSOs), potassium permanganate (KMnO4) and the like and mixture thereof; preferably Potassium persulfate or sodium persulfate; more preferably Potassium persulfate.
  • the present invention provides an improved process for preparation of compound of Formula VI; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity; preferably about 3 to about 8 parts of the total quantity; more preferably about 3 to about 6 parts of the total quantity.
  • the acid used in the aforementioned process is selected from the group comprising but not limited to an inorganic acid, which is selected from the group comprising but not limited to sulfuric acid, phosphoric acid, oleum, hydro bromic acid, hydrochloric acid and the like and mixture thereof; organic acids, which is selected from the group comprising but not limited to acetic acid, propanoic acid, p- toluene sulfonic acid or benzoic acid and the like and mixture thereof; preferably sulfuric acid or hydrochloric acid; more preferably sulfuric acid.
  • the present invention provides an improved process for preparation of compound of Formula VI; wherein the acid is added in to reaction mass in about 30 min to 4 hrs; preferably about 1 hr to 3 hrs.
  • the suitable organic solvent used in aforementioned process is selected from the group comprising but not limited to ethers, include but are not limited to tetrahydrofuran, dimethyl ether, isopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like; esters, include but are not limited to ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and the like; halogenated hydrocarbons include, but are not limited to methylene chloride, ethylene chloride, chloroform and the like; aprotic organic solvent, include but are not limited to N,N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, l,3-dimethyl-2-imidazolidinone, acetonitrile and the like and mixture thereof; preferably tetrahydrofuran, methylene chloride or acetonitrile; more preferably acetonit
  • the present invention provides an improved process for preparation of compound of Formula VI; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity at a temperature of about 0°C to about 60°C; preferably at about 25°C to about 60°C; more preferably about 45°C to about 60°C still more preferably at about 45°C to about 55°C.
  • the present invention provides an improved process for preparation of compound of Formula VI; wherein the total quantity of oxidizing agent is about 0.3 to about 5 equivalents to starting compound of formula V; preferably about 0.5 to about 3 equivalents, more preferably about 1.0 to about 2 equivalents to starting compound of formula V.
  • the present invention provides an improved process for preparation of compound of Formula VI; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity and each part contains about 0.1 to 0.5 equivalents to starting compound of formula V at a temperature of about 0°C to about 60°C.
  • the present invention provides an improved process for preparation of compound of Formula VI; wherein the oxidizing agent is added in about 3 to about 6 parts of the total quantity and each part contains about 0.25 to 0.5 equivalents to starting compound of formula V at a temperature of about 45°C to about 60°C.
  • the reaction temperature may be increased to about 65°C to about reflux; preferably to about 70°C to about 80°C, and then if necessary maintain the reaction for about 15 minutes to about 90 minutes at the same temperature and then allowed for cooling the reaction to 0°C to 60°C, preferably to about 45°C to 55°C for addition of subsequent parts of oxidizing agent as process mentioned above embodiments.
  • the oxidizing agent is added either in one part or two equal parts at higher temperatures such as 70-75°C and this temperature leads to decomposition of the unconsumed oxidizing agent due to highly exothermic nature of the reaction which results incomplete conversion of starting material thereby getting lower yields and starting material contamination.
  • the present invention surprisingly found an alternative procedure to overcome the difficulties associated with the prior art process by adopting multiple part wise addition and predefined quantity of oxidizing agent for each part and at addition of oxidizing agent at lower temperature to avoid the possibility of heat of reaction so that oxidizing agent decomposition is greatly eliminated thereby complete conversion of the starting material and getting higher yields and high pure product.
  • reaction mass After completion of the reaction, optionally water may be added to the reaction mass and then the resultant compound of Formula VI may be isolated from reaction mass by conventional techniques such as solvent extraction, solvent precipitation, and crystallization, concentrated by subjecting the solution to heating, decantation or filtration.
  • the present invention provides compound of Formula Via prepared by the process described as above having a purity of at least about 95%, as measured by HPLC, preferably at least about 97% as measured by HPLC; and content of N -oxide impurity is about 5%, as measured by HPLC, more preferably is about 3% as measured by HPLC.
  • oxidation reaction involved in the conversion of formula V to formula VI there always possibility to formation of N-oxide as impurity and is possibility of formation is higher when the oxidation reaction at higher temperatures.
  • the N-oxide impurity once formed is very difficult to separate from the product due to less polarity difference with the product. Further, the N-oxide impurity formed is reacted in subsequent stages and carries forward to final stages and is very difficult to separate from the final product.
  • N-oxide impurity can be separated from the product by dissolving the compound of Formula VI having N-oxide impurity in a suitable solvent and precipitating the compound of Formula VI by adding an antisolvent to obtain the compound of Formula VI substantially free of N-oxide impurity.
  • the present invention provides a process for preparation of compound of Formula VI having N-oxide impurity less than 0.5% by HPLC, comprising: a) dissolving a compound of Formula VI having about 0.5% or more N-oxide impurity by HPLC in a suitable solvent, b) adding an anti- solvent to the step a) solution, and c) Isolating the compound of Formula VI having N-oxide impurity less than 0.5% by HPLC; wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2- R7 is independently selected from hydrogen, halogen and CM alkyl.
  • the step a) process may be involves dissolving a compound of Formula VI having N- oxide impurity more than 0.5% by HPLC in a suitable solvent at a temperature of about ambient temperature to reflux temperature; preferably at about 40°C to about 75°C; more preferably at about 55°C to about 65°C
  • the suitable solvent used to dissolve compound of Formula VI wherein the “Rl” is selected from hydrogen or C alkyl, preferably methyl or ethyl; and each of R2-R7 is independently selected from hydrogen, halogen and CM alkyl, preferably R2 and R5-R7 are hydrogen, R3 is bromo and R4 is chloro; having about 0.5% or more N-oxide impurity by HPLC is selected from the group comprising but not limited to amides include, but are not limited to dimethylacetamide, dimethylformamide, N- methylpyrrolidone and the like; esters include, but are not limited to ethyl acetate, methyl acetate and the like; ketones include, but are not limited to acetone, methyl isobutyl ketone, methyl ethyl ketone and the like; nitriles include, but are not limited to acetonitrile, propionitrile and the like; halogenated hydrocarbons include, but are not limited to
  • the anti-solvent used in aforementioned step b) process is selected from the group comprising but not limited to ethers include, but are not limited to tetrahydrofuran, methyl tetrahydrofuran, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like; aliphatic and alicyclic hydrocarbons include, but are not limited to hexane, heptane, pentane, cyclohexane, cycloheptane, cyclopentane and the like and mixture thereof; water and mixture thereof; preferably hexane, cyclohexane or water; more preferably water.
  • ethers include, but are not limited to tetrahydrofuran, methyl tetrahydrofuran, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dio
  • the pure compound of Formula VI having N-oxide impurity less than 0.5% by HPLC may be isolated from reaction mass by conventional techniques such as solvent extraction, solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration; preferably by filtration.
  • the compound of Formula VI obtained by the purification processes described as above having purity of at least about 98% as measured by HPLC, preferably at least about 99% as measured by HPLC and substantially free of N-oxide impurity; wherein the word “substantially free” refers to compound of Formula VI having less than 1 % of N-oxide impurity as measured by HPLC, preferably less 0.5 % of N-oxide impurity as measured by HPLC.
  • the present invention provides an improved process for the preparation of anthranilamide compounds such as chlorantraniliprole and/or cyantraniliprole, comprising preparing the compound of Formula VI as process described above, and converting the compound of Formula VI in to chlorantraniliprole or cyantraniliprole by any process known in the art for example W02006/062978, W02004/067528 or by the process described in the present specification.
  • the present invention provides a composition comprising anthranilamide compounds such as chlorantraniliprole and/or cyantraniliprole, prepared by the process of the compound of Formula IV and/ or compound of Formula VI by the present invention and/or at least one excipient.
  • anthranilamide compounds such as chlorantraniliprole and/or cyantraniliprole
  • the present invention relates to a process for preparation of compound of Formula VI, which is depicted in below scheme: wherein the “Rl” is selected from hydrogen or CM alkyl; and each of R2-R7 is independently selected from hydrogen, halogen and C alkyl.
  • the present invention relates to a process for preparation of compound of Formula Via, which is depicted in below scheme:
  • the present invention provides chlorantraniliprole or cyantraniliprole and its intermediates, obtained by the above process, as analyzed using high performance liquid chromatography (“HPLC”) with Zorbax RX-C8 column and buffer acetonitrile and water as mobile phase with flow rate of about 1.0 mL/min.
  • HPLC high performance liquid chromatography
  • reaction mass was allowed to cool to 25-35°C, filtered and washed with water (100 mL) and dried the wet material under vacuum at 60-65°C to obtain title compound.
  • Wt 120 gm; Purity by HPLC: 99.3%.
  • Triphosgene (80 gm) and methylene chloride (700 mL) were added in to a round bottom flask at 25-35°C and stirred for 10-20 min at same temperature.
  • To the reaction mass compound of Formula II (100 gm) and sodium bicarbonate (135.7 gm) were added at 25-35°C and was stirred for 6 hrs at same temperature. After completion of the reaction, reaction mass was allowed to cool to 10-15°C and 40% aqueous monomethylamine (63 gm) was added at same temperature. Further, reaction mass was heated to 25-35°C and stirred for 3 hrs at same temperature. After completion of the reaction, to the reaction mass water (600 mL) was added and concentrated under vacuum at 45-55°C.
  • reaction mass was allowed to cool to 25-35°C, methanol (100 mL) was added and stirred for 2-3 hrs at same temperature. Filtered the solids and washed the wet cake with water (100 mL) and dry the wet material initially at 25-35°C for 60 min, then dry at 60- 75°C for 6 hr to obtain title compound.
  • Wt 104 gm; Purity by HPLC: 99.5%.
  • reaction mass was heated to 25-35°C and stirred for 3 hrs at same temperature. After completion of the reaction, to the reaction mass water (600 mL) was added and concentrated under vacuum at 45-55°C. Then the reaction mass was allowed to cool to 25-35°C, methanol (100 mL) was added and stirred for 2-3 hrs at same temperature. Filtered the solids and washed the wet cake with water (100 mL) and dry the wet material initially at 25-35°C for 60 min, then dry at 60-75°C for 6 hr to obtain title compound. Wt: 100 gm.
  • Reaction mass was allowed to cool to 45-55°C and third part of potassium persulfate (4.78 g) was added at same temperature. Reaction mass was heated to 72-78°C and stirred for 1 hr at same temperature. After completion of the reaction, temperature was cool to 55-65°C and water (48 mL) was added at same temperature. Then the product containing organic layer and aqueous layers were separated at 55- 65°C. Back extract the aqueous layer with acetonitrile (12 mL). To the combined organic layer water (36 mL) was added at 55-65°C, cool to 25-35°C and stirred for 3 hrs.
  • Reaction mass was allowed to cool to 45-55°C and third part of potassium persulfate (3.59 g) was added at same temperature. Reaction mass was heated to 72-78°C and stirred for 1 hr at same temperature. Reaction mass was allowed to cool to 45-55°C and fourth part of potassium persulfate (3.59 g) was added at same temperature. Reaction mass was heated to 72-78°C and stirred for 1 hr at same temperature. After completion of the reaction, temperature was cool to 55-65°C and water (48 mL) was added at same temperature. Then the product containing organic layer and aqueous layers were separated at 55-65°C. Back extract the aqueous layer with acetonitrile (12 mL).
  • Reaction mass was further heated to 72-78°C and allowed to stirred for 1 hr at same temperature. Reaction mass was allowed to cool to 45-55°C and third part of potassium persulfate (23.9 g; 0.24 mole) was added at same temperature. Reaction mass was further heated to 72-78°C and allowed to stirred for 1 hr at same temperature. Reaction mass was allowed to cool to 45-55°C and fourth part of potassium persulfate (23.9 g; 0.24 mole) was added at same temperature. Reaction mass was further heated to 72-78°C and allowed to stirred for 1 hr at same temperature.
  • Reaction mass was allowed to cool to 45-55°C and fifth part of potassium persulfate (47.8 g; 0.49 mole) was added at same temperature. Reaction mass was further heated to 72-78°C and allowed to stirred for 1 hr at same temperature. After completion of the reaction, temperature was cool to 40- 50°C and water (480 mL) was added at same temperature. Reaction mass was heated to 60-70°C and stirred for 10-20 min at same temperature. Then the product containing organic layer and aqueous layers were separated at 60-70°C. Back extract the aqueous layer with acetonitrile (120 ml). To the combined organic layer water (360 mL) was added in 30 min at ⁇ 60°C.
  • acetonitrile 120 ml
  • Reaction mass was allowed to cool to 45-55°C and third part of potassium persulfate (11.95 g) was added at same temperature. Reaction mass was heated to 72-78°C and stirred for 1 hr at same temperature. Reaction mass was allowed to cool to 45-55°C and fourth part of potassium persulfate (11.95g) was added at same temperature. Reaction mass was heated to 72-78°C and stirred for 1 hr at same temperature. Reaction mass was allowed to cool to 45-55°C and fifth part of potassium persulfate (11.95 g) was added at same temperature. Reaction mass was heated to 72- 78°C and stirred for 1 hr at same temperature.
  • Reaction mass was allowed to cool to 45- 55°C and sixth part of potassium persulfate (11.95 g) was added at same temperature. Reaction mass was heated to 72-78°C and stirred for 1 hr at same temperature. After completion of the reaction, temperature was cool to 55-65°C and water (240 mL) was added at same temperature. Then the product containing organic layer and aqueous layers were separated at 55-65°C. Back extract the aqueous layer with acetonitrile (60 ml). To the combined organic layer water (180 mL) was added at ⁇ 65°C, cool to 25- 35°C and stirred for 3 hrs at same temperature.
  • acetonitrile 60 ml
  • the starting material compound of Formula Va was around 90% and the product formation is around 8.4% after 4 hours of reaction maintenance at 80°C. Reaction was not completed due to decomposition of potassium persulfate at higher temperatures.
  • the starting material compound of Formula la was around 10% and the product formation is around 74 % after 4 hours of reaction maintenance at reflux. Reaction was not completed due to decomposition of potassium persulfate at higher temperatures.

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Abstract

La présente invention concerne des procédés pour préparer un composé de 2-amino-5-chloro-N-3-diméthylbenzamide de formule (IV) et un composé de pyrazole-carboxylate de formule (VI), un intermédiaire utile pour la préparation de certains composés d'anthranilamide, par exemple le chlorantraniliprole et/ou le cyantraniliprole, "R1" étant choisi parmi un hydrogène ou un alkyle en C1-4 ; et R2 à R7 étant chacun choisis indépendamment parmi un hydrogène, un halogène et un alkyle en C1-4.
PCT/IB2022/059981 2021-10-28 2022-10-18 Procédés de préparation de composés intermédiaires de pyrazole-carboxylate et d'anthranilamide WO2023073502A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006068669A1 (fr) * 2004-07-26 2006-06-29 E.I. Dupont De Nemours And Company Melanges d'agents de lutte contre les nuisibles invertebres a base d'anthranilamide
WO2008070158A1 (fr) * 2006-12-06 2008-06-12 E. I. Du Pont De Nemours And Company Procédé de préparation de produits dérivés de l'acide 2-amino-5-cyanobenzoïque
CN103539694A (zh) * 2013-09-12 2014-01-29 中国农业科学院植物保护研究所 一种多取代菊酰苯胺类衍生物及其应用
WO2021086957A1 (fr) * 2019-11-01 2021-05-06 Fmc Corporation Nouveau procédé efficace de synthèse de 2-amino-5-chloro-n-,3-diméthylbenzamide

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006068669A1 (fr) * 2004-07-26 2006-06-29 E.I. Dupont De Nemours And Company Melanges d'agents de lutte contre les nuisibles invertebres a base d'anthranilamide
WO2008070158A1 (fr) * 2006-12-06 2008-06-12 E. I. Du Pont De Nemours And Company Procédé de préparation de produits dérivés de l'acide 2-amino-5-cyanobenzoïque
CN103539694A (zh) * 2013-09-12 2014-01-29 中国农业科学院植物保护研究所 一种多取代菊酰苯胺类衍生物及其应用
WO2021086957A1 (fr) * 2019-11-01 2021-05-06 Fmc Corporation Nouveau procédé efficace de synthèse de 2-amino-5-chloro-n-,3-diméthylbenzamide

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