GW-577

Chemical Name: 7-Bromo-3(S)-butyl-3-ethyl-8-hydroxy-5-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepine-1,1-dioxide
CAS No. 179410-97-0 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The monosilylation of 2-butyl-2-ethylpropane-1,3-diol (I) with TBDMS-Cl and NaH in THF gives silyl ether (II),which is oxidized with NaIO4 and RuCl3 in CCl4/acetonitrile/water yielding silylated hexanoic acid (III).Elimination of the silyl group of (III) with tetrabutylammonium fluoride (TBAF) affords the hydroxyacid (IV),which is treated with refluxing 48% HBr to give the 2-(bromomethyl)-2-ethylhexanoic acid (V).The condensation of (V) with 2-amino-methoxythiophenol (VI) by means of triethylamine or pyrrolidine in DMF provides intermediate (VII),which is cyclized by means of p-toluenesulfonic acid in refluxing tetradecane to give the 1,5-benzothiazepinone (VIII).The reaction of (VIII) with N-bromosuccinimide (NBS) in dichloromethane yields the 7-bromo derivative (IX),which is treated with bromobenzene (X),K2CO3 and CuBr to afford the 5-phenylbenzothiazepinone (XI).The reduction of the carbonyl group of (XI) with LiAlH4 in ethyl ether gives the benzothiazepine (XII),which is then oxidized with OsO4 in THF/ tert-butanol yielding the S,S-dioxide (XIII).Finally,this compound is demethylated with AlBr3 and ethanethiol in dichloromethane.