Preparing propranolol or its hydrochloride salt, used for treating multiple indications e.g. hypertension, by treating propranolol with reagent selected from e.g. dimethylamino hydrochloride, treating pure propranolol with hydrochloric acid, and isolating propranolol or its hydrochloride salt
	BHARGUDE P L; KAWTHEKAR R B; CRASTA S; SHEKHAWAT R S; PALLE V R A
	2023-08-22
专利权人	GLENMARK LIFE SCI LTD (GLMK-C)
申请日期	2023-08-22
专利号	IN202321056337-A
成果简介	NOVELTY - Preparing propranolol (II) or its hydrochloride salt (propranolol hydrochloride (I)) involves (a) treating propranolol (II) with a reagent selected from the dimethylamino hydrochloride, ascorbic acid and sodium ascorbate to obtain pure propranolol (II); (b) treating the pure propranolol (II) obtained with hydrochloric acid to obtain its hydrochloride salt, i.e. propranolol hydrochloride (I); and (c) isolating propranolol (II) from the step (a) or its hydrochloride salt (I) from the step (b); where the resulting propranolol or propranolol hydrochloride comprises 0.01-0.05 ppm of N-nitrosamine impurity (III). USE - Method for preparing propranolol (II) or its hydrochloride salt (propranolol hydrochloride (I)), that used for the treatment of multiple indications such as hypertension, angina pectoris caused due to coronary atherosclerosis, migraine and hypertrophic subaortic stenosis. No biological data is given. ADVANTAGE - The method is capable of reducing or preventing the formation of nitrosamine impurities in simple and cost-effective manner. DETAILED DESCRIPTION - Preparing propranolol of formula (II) or its hydrochloride salt (propranolol hydrochloride of formula (I)), involves (a) treating propranolol (II) with a reagent selected from the dimethylamino hydrochloride, ascorbic acid and sodium ascorbate to obtain pure propranolol (II); (b) treating the pure propranolol (II) obtained with hydrochloric acid to obtain its hydrochloride salt, i.e. propranolol hydrochloride (I); and (c) isolating propranolol (II) from the step (a) or its hydrochloride salt (I) from the step (b); where the resulting propranolol or propranolol hydrochloride comprises 0.01-0.05 ppm of N-nitrosamine impurity of formula (III). INDEPENDENT CLAIMS are included for: 1. a method for the preparing pure propranolol (II) or its hydrochloride salt (I) which involves: (a) preparing a solution of propranolol (II) in a solvent; (b) treating the solution of the step (a) with a reagent; (c) heating the reaction mass of the step (b) at a temperature ranging from 40-90 ℃; (d) cooling the reaction mass of the step (c) to a temperature ranging from 20-0℃ to obtain propranolol (II); (e) treating the reaction mass of the step (d) with hydrochloric acid to obtain its hydrochloride salt (I); and (f) isolating propranolol (II) from the step (d) or its hydrochloride salt (I) from the step (e); or, (a) reacting 1-naphthol of formula (VI) with epichlorohydrin of formula (VII) in the presence of triethylamine to obtain 1-chloro-3-(naphthalene-1- yloxy)propan-2-ol of formula (X); (b) reacting the compound (X) obtained in the step (a) without isolating it with sodium hydroxide to obtain 2- 5 ((naphthalene-1-yloxy)methyl)oxirane of formula (IV); (c) reacting the compound (IV) obtained in the step (b) without isolating it with isopropyl amine to obtain propranolol (II); (d) preparing a solution of propranolol (II) obtained in the step (c) in water or an organic solvent or its mixture; and treating it with a reagent; (e) heating the reaction mass of the step (d) at a temperature ranging from 40-90 ℃; (f) cooling the reaction mass of the step (e) to a temperature ranging from 20-0 ℃ to obtain propranolol (II); (g) treating the reaction mass of the step (f) with hydrochloric acid to obtain its hydrochloride salt (I); and (h) isolating propranolol (II) as obtained in step (f) or propranolol hydrochloride (I) as obtained in step (g); 2. a propranolol (II) is prepared by the method; and 3. a propranolol hydrochloride (I) is prepared by the method.
IPC 分类号	A61K-031/138 ; A61K-047/12 ; A61K-047/18 ; A61K-047/26 ; A61K-009/22 ; C07C-213/08 ; C07C-213/10 ; C07C-217/30
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/20740
专题	中国科学院新疆生态与地理研究所
作者单位	GLENMARK LIFE SCI LTD (GLMK-C)
推荐引用方式 GB/T 7714	BHARGUDE P L,KAWTHEKAR R B,CRASTA S,et al. Preparing propranolol or its hydrochloride salt, used for treating multiple indications e.g. hypertension, by treating propranolol with reagent selected from e.g. dimethylamino hydrochloride, treating pure propranolol with hydrochloric acid, and isolating propranolol or its hydrochloride salt. IN202321056337-A[P]. 2023.

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