【结 构 式】 |
【药物名称】RS-1653 【化学名称】2-(4-Fluoro-7-methyl-1,2-benzisoxazol-3-yloxy)ethanamine hydrochloride 【CA登记号】178746-70-8, 178746-69-5 (free base) 【 分 子 式 】C10H12ClFN2O2 【 分 子 量 】246.67074 |
【开发单位】Sankyo (Originator) 【药理作用】Antiparkinsonian Drugs, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, MAO-A Inhibitors, MAO-B Inhibitors |
合成路线1
Methyl 2,6-difluorobenzoate (I) was converted to the hydroxamic acid (II) upon treatment with hydroxylamine and KOH. Cyclization of the fluorobenzohydroxamic acid (II) using KOH in boiling butanol produced the 3-hydroxybenzisoxazole (III), which was subjected to Mitsunobu coupling with N-Boc-ethanolamine (IV) to furnish the N-Boc-aminoethyl ether (V). Metalation of (V) with butyllithium at -70 C, followed by quenching with iodomethane gave rise to two regioisomeric methylbenzisoxazoles (VI) and (VII), which were separated by column chromatography. The target 7-methyl benzisoxazole (VII) was then deprotected under acidic conditions to yield the title aminoethoxy derivative.
【1】 Kojima, K.; Aizawa, Y.; Kaneko, I.; Sakai, J.; Kozuka, M.; Koyama, K.; Samata, N.; Yoshimi, K. (Sankyo Co., Ltd.); Isoxazoles. EP 0779281; JP 1997059264; US 5965591; US 6096771; WO 9606837 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 58771 | 2,6-Difluorobenzoic acid methyl ester; Methyl 2,6-difluorobenzoate | 13671-00-6 | C8H6F2O2 | 详情 | 详情 |
(II) | 58772 | 2,6-difluoro-N-hydroxybenzamide | C7H5F2NO2 | 详情 | 详情 | |
(III) | 58773 | 4-fluoro-1,2-benzisoxazol-3-ol | C7H4FNO2 | 详情 | 详情 | |
(IV) | 32500 | tert-butyl 2-hydroxyethylcarbamate | 26690-80-2 | C7H15NO3 | 详情 | 详情 |
(V) | 58774 | tert-butyl 2-[(4-fluoro-1,2-benzisoxazol-3-yl)oxy]ethylcarbamate | C14H17FN2O4 | 详情 | 详情 | |
(VI) | 58775 | tert-butyl 2-[(4-fluoro-5-methyl-1,2-benzisoxazol-3-yl)oxy]ethylcarbamate | C15H19FN2O4 | 详情 | 详情 | |
(VII) | 58776 | tert-butyl 2-[(4-fluoro-7-methyl-1,2-benzisoxazol-3-yl)oxy]ethylcarbamate | C15H19FN2O4 | 详情 | 详情 |