JTV-519, K-201

4-[3-(4-苯甲基哌啶-1-基)丙酰]-7-甲氧基-2,3,4,5-四氢-1,4-苯并硫氮杂卓Chemical Name: 4-[3-(4-Benzylpiperidin-1-yl)propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine
CAS No. 145903-06-6
项目整合开发状态: Phase II
项目研究机构: Japan Tobacco (Originator), Kirin Brewery (Originator)
合成路线:Treatment of 2,5-dihydroxybenzoic acid (I) with dimethyl sulfate and K2CO3 afforded methyl 2-hydroxy-5-methoxybenzoate (II).Condensation of (II) with dimethylthiocarbamoyl chloride gave the O-aryl thiocarbamate (III),which underwent thermal rearrangement to the S-aryl isomer (IV) upon heating at 265 C in diphenyl ether.Subsequent hydrolysis of the thiocarbamate group of (IV) furnished the desired thiophenol compound (V).Cyclization of the mercapto ester (V) with 2-chloroethylamine (VI) gave rise to the benzothiazepinone (VII),which was further reduced to the benzothiazepine (VIII) using LiAlH4.Acylation of (VIII) with acryloyl chloride (IX) provided the acrylamide (X).Finally,Michael addition of 4-benzylpiperidine (XI) to acrylamide (X) yielded the title compound.