Preparing remimazolam besylate for treating sedation, by reacting methyl-3-(bromo-2-oxo-(pyridin-2-yl)-2,3-dihydro-1H-benzo [e] [1,4] diazepin-3-yl) propanoate, cyclizing bromo-2-((2,2-dimethoxypropyl)amino)-(pyridin-2-yl)-3H-benzo[e] [1,4]diazepin-3-yl) propanoate and purifying
	ZANJE P H; PAWAR S S; ATKURU V S; PATIL D J
	2022-09-23
专利权人	ENALTEC LABS PRIVATE LTD (ENAL-Non-standard)
申请日期	2022-09-23
专利号	IN202221054689-A
成果简介	NOVELTY - Preparing remimazolam besylate (I) comprises: (a) reacting (S)-methyl-3-(7-bromo-2-oxo-5-(pyridin-2-yl)-2,3-dihydro-1H-benzo [e] [1,4] diazepin-3-yl) propanoate (V) with 2-bromopyridine in the presence of at least one carbonyl activating agent to obtain a compound (IV); (b) reacting compound (IV) with amino ketal compound to obtain (S)-methyl-3-(7- bromo-2-((2,2-dimethoxypropyl)amino)-5-(pyridin-2-yl)-3H-benzo[e] [1,4]diazepin-3-yl) propanoate (III); (c) deprotecting and cyclizing the obtained compound (III) to obtain remimazolam base (II); (d) converting remimazolam base (II) into crude remimazolam besylate (I); and (e) purifying the crude remimazolam besylate (I) to obtained pure remimazolam besylate (I). USE - Method for preparing remimazolam besylate for treating sedation, hypnosis, convulsions, induction of anxiolysis, and muscle relaxation. No biological data given. ADVANTAGE - The method avoids the formation of impurities and effectively remove the impurities, provides the product with high yield, purity and with known individual impurity less than 0.15%, and is simple, economic, safe. The remimazolam besylate has HPLC purity of greater than 99.70% and Chiral HPLC Purity of greater than 99.90% without chromatographic purification, and has high chemical or polymorphic purity, flowability, solubility, dissolution rate, bioavailability, morphology or crystal habit, stability such as chemical stability i.e. thermal and mechanical stability with respect to polymorphic conversion, stability towards dehydration and/or storage stability, a lower degree of hygroscopicity, low content of residual solvents, adhesive tendencies and advantageous processing and handling characteristics such as compressibility, and bulk density. DETAILED DESCRIPTION - Preparing remimazolam besylate of formula (I) comprises: (a) reacting (S)-methyl-3-(7-bromo-2-oxo-5-(pyridin-2-yl)-2,3-dihydro-1H-benzo [e] [1,4] diazepin-3-yl) propanoate of formula (V) with 2-bromopyridine in the presence of at least one carbonyl activating agent to obtain a compound of formula (IV); (b) reacting compound (IV) with amino ketal compound to obtain (S)-methyl-3-(7- bromo-2-((2,2-dimethoxypropyl)amino)-5-(pyridin-2-yl)-3H-benzo[e] [1,4]diazepin-3-yl) propanoate of formula (III); (c) deprotecting and cyclizing the obtained compound (III) to obtain remimazolam base of formula (II); (d) converting remimazolam base (II) into crude remimazolam besylate (I); and (e) purifying the crude remimazolam besylate (I) to obtained pure remimazolam besylate (I). R=CH3, p-toluene or phenyl. INDEPENDENT CLAIMS are included for: 1. a compound remimazolam mesylate (I) having individual impurity less than 0.15% obtained by reacting the remimazolam besylate (I) with base in an organic solvent to obtain remimazolam base (II); isolating remimazolam base (II); and converting remimazolam base into pure remimazolam besylate (I) in presence of alcoholic solvent; and 2. a compound of (IV).
IPC 分类号	A61K-031/5517 ; C07C-231/14 ; C07D-243/18 ; C07D-277/58 ; C07K-007/54
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/22482
专题	中国科学院新疆生态与地理研究所
作者单位	ENALTEC LABS PRIVATE LTD (ENAL-Non-standard)
推荐引用方式 GB/T 7714	ZANJE P H,PAWAR S S,ATKURU V S,et al. Preparing remimazolam besylate for treating sedation, by reacting methyl-3-(bromo-2-oxo-(pyridin-2-yl)-2,3-dihydro-1H-benzo [e] [1,4] diazepin-3-yl) propanoate, cyclizing bromo-2-((2,2-dimethoxypropyl)amino)-(pyridin-2-yl)-3H-benzo[e] [1,4]diazepin-3-yl) propanoate and purifying. IN202221054689-A[P]. 2022.

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