Preparing Avacopan involves reacting ethyl chloronicotinate compound with tertiary butoxy oxoethyl phenyl boronic acid compound in presence of suitable reagents and solvent, and reacting with suitable reagent and solvent to provide ethyl tertiary butoxy oxoethyl phenyl nicotinate compound
	KUMAR M A; PRADEEP R; RAMPRASAD A K; NAGARAJU C
	2023-09-27
专利权人	MAITHRI DRUGS PRIVATE LTD (MAIT-Non-standard)
申请日期	2023-09-27
专利号	IN202341064885-A
成果简介	NOVELTY - Preparing Avacopan involves reacting ethyl 2-chloronicotinate compound (I) with (4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)boronic acid compound (II) in presence of suitable reagents and solvent to provide ethyl 2-(4-(2-(tert-butoxy)-2-oxoethyl)phenyl)nicotinate compound (III). The obtained ethyl 2-(4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)nicotinate compound (III) is reacted with suitable reagent and solvent to provide ethyl 2-(4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)nicotinate compound (IV) or its salt. The obtained ethyl 2-(4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)nicotinate compound (IV) is reacted with (2-fluoro-6-methylbenzoyl chloride) using the suitable reagents and solvents to provide tert.-butyl (Z)-(4-(1-(2-fluoro-6-methylbenzoyl)-3-(1-methoxyprop-1-en-1-yl)piperidin-2-yl)phenyl)carbamate compound (V) or its salt. USE - Method for preparing (2R,3S)-2-[4-(cyclopentyl amino) phenyl]-1-(2-fluoro-6-methylbenzoyl)-N-[4-methyl-3-(trifluoromethyl)phenyl]-3-piperidine carboxamide (Avacopan) of formula (IX), or its amorphous and crystalline forms (all claimed). ADVANTAGE - The method provides an enhanced procedure to produce avacopan, involves uncomplicated experimental steps suitable for large-scale manufacturing, eliminates the need for column chromatography purification while ensuring the generation of highly pure avacopan, addresses concerns by offering improved techniques for avacopan synthesis, its intermediary components, and related salts by their efficiency, feasibility for industrial application, and cost-effectiveness. DETAILED DESCRIPTION - Preparing Avacopan involves reacting ethyl 2-chloronicotinate compound of formula (I) with (4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)boronic acid compound of formula (II) in presence of suitable reagents and solvent to provide ethyl 2-(4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)nicotinate compound of formula (III). The obtained ethyl 2-(4-(2-(tert-butoxy)-2-oxoethyl)phenyl)nicotinate compound (III) is reacted with suitable reagent and solvent to provide ethyl 2-(4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)nicotinate compound of formula (IV) or its salt. The obtained ethyl 2-(4-(2-(tert.-butoxy)-2-oxoethyl)phenyl)nicotinate compound of formula (IV) is reacted with (2-fluoro-6-methylbenzoyl chloride) using the suitable reagents and solvents to provide tert-butyl (Z)-(4-(1-(2-fluoro-6-methylbenzoyl)-3-(1-methoxyprop-1-en-1-yl)piperidin-2-yl)phenyl)carbamate compound of formula (V) or its salt. The compound (V) is deprotected with a suitable reagent and solvent to provide (Z)-(2-(4-aminophenyl)-3-(1-methoxyprop-1-en-1-yl)piperidin-1-yl)(2-fluoro-6-methylphenyl)methanone compound of formula (VI) or salts. The compound (VI) is reacted with cyclopentanone in the presence of suitable reagents and solvents to provide pure (Z)-(2-(4-(cyclopentylamino)phenyl)-3-(1-methoxyprop-1-en-1-yl)piperidin-1-yl)(2-fluoro-6-methylphenyl)methanone of formula (VII). The obtained compound (VII) is hydrolyzed with suitable reagents to get (Z)-(2-(4-(cyclopentylamino)phenyl)-3-(1-hydroxyprop-1-en-1-yl)piperidin-1-yl)(2-fluoro-6-methylphenyl)methanone compound of formula (VIII), optionally purifying by using suitable acid and base solvent. The compound (VIII) is reacted with compound 4-methyl-3-(trifluoromethyl)aniline using suitable reagents and solvents to provide pure compound of formula (IX). Optionally, the compound of formula (VII) is reacted with 4-methyl-3-(trifluoromethyl)aniline in presence of suitable solvents and reagents to provide Avacopan (IX) as target compound. INDEPENDENT CLAIMS are also included for the following: (1) a method for producing amorphous form of compound (IX), which involves stirring the compound (IX) in dichloromethane, and then evaporating the obtained solution to get the pure amorphous form of compound (IX); and (2) a method for crystalline form of compound (IX), which involves stirring the compound (IX) in methanol at 45-55℃, and then filtering the pure crystalline form to get the pure crystalline form of compound (IX).
IPC 分类号	A61P-029/00 ; C07D-221/00 ; C07D-401/12 ; C07D-405/14 ; C12N-009/06 ; C12P-013/00 ; C12P-017/12
国家	印度
专业领域	医药卫生
语种	英语
成果类型	专利
文献类型	科技成果
条目标识符	http://119.78.100.226:8889/handle/3KE4DYBR/20216
专题	中国科学院新疆生态与地理研究所
作者单位	MAITHRI DRUGS PRIVATE LTD (MAIT-Non-standard)
推荐引用方式 GB/T 7714	KUMAR M A,PRADEEP R,RAMPRASAD A K,et al. Preparing Avacopan involves reacting ethyl chloronicotinate compound with tertiary butoxy oxoethyl phenyl boronic acid compound in presence of suitable reagents and solvent, and reacting with suitable reagent and solvent to provide ethyl tertiary butoxy oxoethyl phenyl nicotinate compound. IN202341064885-A[P]. 2023.

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