【结 构 式】 |
【分子编号】13427 【品名】2-[(1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-2-naphthalenyl]ethyl 4-methylbenzenesulfonate 【CA登记号】 |
【 分 子 式 】C22H27FO4S 【 分 子 量 】406.5183832 【元素组成】C 65% H 6.69% F 4.67% O 15.74% S 7.89% |
合成路线1
该中间体在本合成路线中的序号:(VII)The condensation of 4-(1-benzyloxy-N-methylformamido)butyric acid (I) with o-phenylenediamine (II) and isobutyl chloroformate (III) by means of triethylamine gives N-[3-[N-(2-aminophenyl)carbamoyl]propyl]-N-methylcarbamic acid benzyl ester (IV), which is cyclized by means of p-toluenesulfonic acid in refluxing toluene to the benzimidazole derivative (V). Hydrogenation of (V) with H2 over Pd/C in methanol affords 2-[3-(methylamino)propyl]benzimidazole (VI), which is condensed with the chiral p-toluenesulfonate (VII) by heating at 120 C to give the chiral tetrahydronaphthol (VIII). Finally, this alcohol is esterified with 2-methoxyacetyl chloride and ethyl diisopropylamine in chloroform.
【1】 Merlos, M.; Castaner, J.; Casa, A.; Graul, A.; Mibefradil Hydrochloride. Drugs Fut 1997, 22, 10, 1091. |
【2】 Branca, Q.; Jaunin, R.; Marki, H.P.; Marti, F.; Ramuz, H. (F. Hoffmann-La Roche AG); Tetrahydronaphthalene derivs. and medicines containing them. EP 0268148; JP 1988139171; US 4808605 . |
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) | 13421 | 4-[[(Benzyloxy)carbonyl](methyl)amino]butyric acid | C13H17NO4 | 详情 | 详情 | |
(II) | 12824 | 2-Aminophenylamine; o-Phenylenediamine; 1,2-Benzenediamine | 95-54-5 | C6H8N2 | 详情 | 详情 |
(III) | 13423 | 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate | 543-27-1 | C5H9ClO2 | 详情 | 详情 |
(IV) | 13424 | benzyl 4-(2-aminoanilino)-4-oxobutyl(methyl)carbamate | C19H23N3O3 | 详情 | 详情 | |
(V) | 13425 | benzyl 3-(1H-benzimidazol-2-yl)propyl(methyl)carbamate | C19H21N3O2 | 详情 | 详情 | |
(VI) | 13426 | N-[3-(1H-Benzimidazol-2-yl)propyl]-N-methylamine; 3-(1H-Benzimidazol-2-yl)-N-methyl-1-propanamine | C11H15N3 | 详情 | 详情 | |
(VII) | 13427 | 2-[(1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-2-naphthalenyl]ethyl 4-methylbenzenesulfonate | C22H27FO4S | 详情 | 详情 | |
(VIII) | 13428 | (1S,2S)-2-[2-[[3-(1H-Benzimidazol-2-yl)propyl](methyl)amino]ethyl]-6-fluoro-1-isopropyl-1,2,3,4-tetrahydro-2-naphthalenol | C26H34FN3O | 详情 | 详情 | |
(IX) | 13429 | 2-Methoxyacetyl chloride; Methoxyacetyl chloride | 38870-89-2 | C3H5ClO2 | 详情 | 详情 |