A new method for the preparation of alololol hydrochloride

Abstract

The invention belongs to the technical field of medicines and particularly relates to a simple and efficient method for preparing selective beta 1 adrenoceptor antagonists 5-[2-[[[3-(1,1-dimethylethyl)amino]-2-hydroxypropyl]thio]-4-thiazolyl]-2-thiophene carboxamide hydrochloride. The method comprises the following steps: firstly, reacting 5-(2-mercapto-4-thiazolyl)-2-thiophenecarboxamide and epoxy chloropropane in the presence of Lewis acid as a catalyst in an organic solvent, after the reaction is completed by the monitoring of TLC, filtering and carrying out pressure reduced concentration to dryness to obtain an intermediate; and secondly, reacting the intermediate and t-butylamine in an organic solvent, cooling to room temperature, adding hydrochloric acid to adjust the pH, carrying out reflux reaction, naturally cooling and crystallizing to obtain arotinolol hydrochloride.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and specifically relates to a simple and efficient method for preparing a selective β1 adrenal receptor antagonist 5-[2-[[[3-(1,1-dimethylethyl)amino]-2- Hydroxypropyl]thio]-4-thiazolyl]-2-thiophenecarboxamide hydrochloride (Arotinolol hydrochloride) method.

[0002] The structural formula of arolol hydrochloride is:

[0003]

[0004] technical background

[0005] Arololol hydrochloride, the chemical name is 5-[2-[[[3-(1,1-dimethylethyl)amino]-2-hydroxypropyl]thio]-4-thiazolyl]-2 - Thiophene carboxamide hydrochloride (structural formula shown in above I), mainly used in the treatment of mild to moderate essential hypertension, angina pectoris, tachyarrhythmia and essential tremor etc. clinically, and for the treatment of obesity Hypertension does not cause weight gain in patients. The drug is a selective β1 adrenoceptor inhibitor with weak α1-adrenoceptor antagonism. It can inhibit α-adrene...

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