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【结 构 式】 
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【药物名称】 【化学名称】N-(1-Cyano-3-pyrrolidinyl)benzenesulfonamide 【CA登记号】325775-30-2 【 分 子 式 】C11H13N3O2S 【 分 子 量 】251.30916 |
【开发单位】Celera (Originator), Merck & Co. (Originator), Merck Frosst (Originator) 【药理作用】Bone Diseases, Treatment of, Bone Resorption Inhibitors, METABOLIC DRUGS, Treatment of Osteoporosis, Cathepsin K Inhibitors, Cathepsin L Inhibitors |
合成路线1
N-Boc-pyrrolidine-3-carboxylic acid (II) was obtained by saponification of the corresponding methyl ester (I) with NaOH. Curtius rearrangement of acid (II) using diphenyl phosphoazidate, followed by trapping the resultant isocyanate with benzyl alcohol, produced carbamate (III). Deprotection of the benzyl carbamate (III) by hydrogenation over Pd/C gave amine (IV), which was acylated with benzenesulfonyl chloride (V) to form sulfonamide (VI). Removal of the Boc group of (VI) was then effected by treatment with trifluoroacetic acid. The resulting amine (VII) was converted to the title cyanamide by treatment with cyanogen bromide.
| 【1】 Rodan, S.B.; Falgueyret, J.-P.; Wesolowski, G.; Oballa, R.M.; Rydzewski, R.M.; Okamoto, O.; Prasit, P.; Riendeau, D.; Aubin, Y.; Percival, M.D.; Novel, nonpeptidic cyanamides as potent and reversible inhibitors of human cathepsins K and L. J Med Chem 2001, 44, 1, 94. |
| 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) | 46931 | 1-(tert-butyl) 3-methyl 1,3-pyrrolidinedicarboxylate | C11H19NO4 | 详情 | 详情 | |
| (II) | 46932 | 1-(tert-butoxycarbonyl)-3-pyrrolidinecarboxylic acid | C10H17NO4 | 详情 | 详情 | |
| (III) | 46933 | tert-butyl 3-[[(benzyloxy)carbonyl]amino]-1-pyrrolidinecarboxylate | C17H24N2O4 | 详情 | 详情 | |
| (IV) | 46934 | 3-amino-1-N-Boc-pyrrolidine; tert-butyl 3-amino-1-pyrrolidinecarboxylate | C9H18N2O2 | 详情 | 详情 | |
| (V) | 14713 | benzenesulfonyl chloride | 98-09-9 | C6H5ClO2S | 详情 | 详情 |
| (VI) | 46935 | tert-butyl 3-[(phenylsulfonyl)amino]-1-pyrrolidinecarboxylate | C15H22N2O4S | 详情 | 详情 | |
| (VII) | 46936 | N-(3-pyrrolidinyl)benzenesulfonamide | C10H14N2O2S | 详情 | 详情 |