【结 构 式】 |
【分子编号】25880 【品名】7-bromo-3-butyl-3-ethyl-8-methoxy-5-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one 【CA登记号】 |
【 分 子 式 】C22H26BrNO2S 【 分 子 量 】448.42398 【元素组成】C 58.93% H 5.84% Br 17.82% N 3.12% O 7.14% S 7.15% |
合成路线1
该中间体在本合成路线中的序号:(XI)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.
【1】 Brieaddy, L.E.; Handlon, A.L.; Hodgson, G.L. Jr. (Glaxo Wellcome plc); Hypolipidemic benzothiazepines. EP 0792268; JP 1999500102; US 5998400; WO 9616051 . |
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) | 25871 | 2-butyl-2-ethyl-1,3-propanediol | 115-84-4 | C9H20O2 | 详情 | 详情 |
(II) | 25872 | 2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2-ethyl-1-hexanol | C15H34O2Si | 详情 | 详情 | |
(III) | 25873 | 2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2-ethylhexanoic acid | C15H32O3Si | 详情 | 详情 | |
(IV) | 25874 | 2-ethyl-2-(hydroxymethyl)hexanoic acid | C9H18O3 | 详情 | 详情 | |
(V) | 25875 | 2-(bromomethyl)-2-ethylhexanoic acid | C9H17BrO2 | 详情 | 详情 | |
(VI) | 25876 | 2-amino-5-methoxyphenylhydrosulfide; 5-Methoxy-2-aminothiophenol;2-Mercapto-4-methoxyaniline;2-amino-5-methoxybenzenethiol;2-Amino-5-methoxy-1-benzenethiol | 6274-29-9 | C7H9NOS | 详情 | 详情 |
(VII) | 25877 | 2-[[(2-amino-5-methoxyphenyl)sulfanyl]methyl]-2-ethylhexanoic acid | C16H25NO3S | 详情 | 详情 | |
(VIII) | 25878 | 3-butyl-3-ethyl-8-methoxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C16H23NO2S | 详情 | 详情 | |
(IX) | 25879 | 7-bromo-3-butyl-3-ethyl-8-methoxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C16H22BrNO2S | 详情 | 详情 | |
(X) | 13365 | Monobromobenzene; 1-Bromobenzene;Phenylbromide;bromobenzene | 108-86-1 | C6H5Br | 详情 | 详情 |
(XI) | 25880 | 7-bromo-3-butyl-3-ethyl-8-methoxy-5-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C22H26BrNO2S | 详情 | 详情 | |
(XII) | 25881 | 7-bromo-3-butyl-3-ethyl-5-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepin-8-yl methyl ether; 7-bromo-3-butyl-3-ethyl-8-methoxy-5-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepine | C22H28BrNOS | 详情 | 详情 | |
(XIII) | 25882 | 7-bromo-3-butyl-3-ethyl-8-methoxy-5-phenyl-2,3,4,5-tetrahydro-1H-1lambda(6),5-benzothiazepine-1,1-dione | C22H28BrNO3S | 详情 | 详情 |