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【结 构 式】 
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【药物名称】Arotinolol hydrochloride, S-596, Almarl 【化学名称】(±)-5-[2-[[3-(tert-Butylamino)-2-hydroxypropyl]thio]-4-thiazolyl-2-thiophenecarboxamide hydrochloride 【CA登记号】68377-92-4 (free base) 【 分 子 式 】C15H22ClN3O2S3 【 分 子 量 】408.00649 |
【开发单位】Sumitomo Pharmaceuticals (Originator) 【药理作用】Angina pectoris, Treatment of, Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Extrapyramidal Disorders, Treatment of, Hypertension, Treatment of, NEUROLOGIC DRUGS, Tardive Dyskinesia, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, beta-Adrenoceptor Antagonists |
合成路线1
The reaction of 5-carboxy-2-acetylthiophene (I) first with SOCl2 in refluxing toluene, and then with aqueous ammonia gives 5-carbamoyl-2-acetylthiophene (II), which is brominated with Br2 in hot acetic acid yielding 5-carbamoyl-2-bromoacetylthiophene (III). The cyclization of (III) with ammonium dithiocarbamate (A) in refluxing methanol-DMF affords 2-mercapto-4-(5'-carbamoyl-2'-thienyl)thiazole (IV), which is finally condensed with 1-chloro-3-tert-butylaminoisopropanol (V) by means of NaOH in water methanol.
| 【1】 Hara, Y.; et al.; Synthesis and beta-adrenergic blocking action of a new thiazolylthiopropanolamine derivative. J Pharm Sci 1978, 67, 1334-35. |
| 【2】 Hibino, T.; et al.; JP 7525562 . |
| 【3】 Hibino, T.; et al.; JP 7576069 . |
| 【4】 Hibino, T.; et al. (Sumitomo Chemical Co., Ltd.); Thiazole derivatives. DE 2341753; FR 2196162; GB 1435139; NL 7311248; US 3932400 . |
| 【5】 Reiner, A. (SkyePharma AG); Process for preparing ursodeoxycholic acid derivates and their inorganic and organic salts having therapeutic activity. EP 0272462 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 33253 | ammonium carbamodithioate | CH6N2S2 | 详情 | 详情 | |
| (I) | 33250 | 5-acetyl-2-thiophenecarboxylic acid | 4066-41-5 | C7H6O3S | 详情 | 详情 |
| (II) | 33251 | 5-acetyl-2-thiophenecarboxamide | C7H7NO2S | 详情 | 详情 | |
| (III) | 33252 | 5-(2-bromoacetyl)-2-thiophenecarboxamide | C7H6BrNO2S | 详情 | 详情 | |
| (IV) | 33254 | 5-(2-sulfanyl-1,3-thiazol-4-yl)-2-thiophenecarboxamide | C8H6N2OS3 | 详情 | 详情 | |
| (V) | 31720 | 1-(tert-butylamino)-3-chloro-2-propanol | C7H16ClNO | 详情 | 详情 |