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【结 构 式】 
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【分子编号】25935 【品名】4-(tert-butoxycarbonyl)-1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C17H24N2O7S 【 分 子 量 】400.45284 【元素组成】C 50.99% H 6.04% N 7% O 27.97% S 8.01% |
合成路线1
该中间体在本合成路线中的序号：(IV)The selective protection of piperazine-2-carboxylic acid (I) with tert-butoxycarbonyl anhydride gives the carbamate (II), which is sulfonated with 4-methoxybenzenesulfonyl chloride (II) and triethylamine yielding the sulfonamide (IV). The esterification and simultaneous deprotection of (IV) with SOCl2 and methanol affords the methyl ester (V), which is treated with benzyl chloroformate (VI) and triethylamine to afford the benzyloxycarbonyl derivative (VII). Finally, this compound is treated with KOH and hydroxylamine in methanol to provide the target hydroxamic acid.
| 【1】 Pikul, S.; Natchus, M.G.; Cheng, M.; et al.; Design and synthesis of piperazine-based MMP inhibitors. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 044. |
| 【2】 De, B.; Natchus, M.G.; Pikul, S.; Almstead, N.G.; Matthews, R.S.; Taiwo, Y.O.; Cheng, M. (The Procter & Gamble Co.); 1,4-Heterocyclic metalloprotease inhibitors. EP 0923563; EP 0925287; WO 9808825; WO 9808827 . |
| 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) | 25933 | 2-piperazinecarboxylic acid; Piperazine-2-carboxylic acid | C5H10N2O2 | 详情 | 详情 | |
| (II) | 25934 | 4-(tert-butoxycarbonyl)-2-piperazinecarboxylic acid | C10H18N2O4 | 详情 | 详情 | |
| (III) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |
| (IV) | 25935 | 4-(tert-butoxycarbonyl)-1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylic acid | C17H24N2O7S | 详情 | 详情 | |
| (V) | 25936 | methyl 1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylate | C13H18N2O5S | 详情 | 详情 | |
| (VI) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (VII) | 25938 | 1-benzyl 3-methyl 4-[(4-methoxyphenyl)sulfonyl]-1,3-piperazinedicarboxylate | C21H24N2O7S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The selective protection of piperazine-2-carboxylic acid (I) with tert-butoxycarbonyl anhydride gives the carbamate (II), which is sulfonated with 4-methoxybenzenesulfonyl chloride (II) and triethylamine yielding the sulfonamide (IV). The esterification and simultaneous deprotection of (IV) with SOCl2 and methanol affords the methyl ester (V), which is treated with phosgene and N-benzyl-N-methylamine (VI) to afford the cyclic urea derivative (VII). Finally, this compound is treated with KOH and hydroxylamine in methanol to provide the target hydroxamic acid.
| 【1】 De, B.; Natchus, M.G.; Pikul, S.; Almstead, N.G.; Matthews, R.S.; Taiwo, Y.O.; Cheng, M. (The Procter & Gamble Co.); 1,4-Heterocyclic metalloprotease inhibitors. EP 0923563; EP 0925287; WO 9808825; WO 9808827 . |
| 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) | 25933 | 2-piperazinecarboxylic acid; Piperazine-2-carboxylic acid | C5H10N2O2 | 详情 | 详情 | |
| (II) | 25934 | 4-(tert-butoxycarbonyl)-2-piperazinecarboxylic acid | C10H18N2O4 | 详情 | 详情 | |
| (III) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |
| (IV) | 25935 | 4-(tert-butoxycarbonyl)-1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylic acid | C17H24N2O7S | 详情 | 详情 | |
| (V) | 25936 | methyl 1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylate | C13H18N2O5S | 详情 | 详情 | |
| (VI) | 11969 | N-Methyl(phenyl)methanamine; N-Benzyl-N-methylamine; N-Methylbenzylamine | 103-67-3 | C8H11N | 详情 | 详情 |
| (VII) | 25937 | methyl 4-[[benzyl(methyl)amino]carbonyl]-1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylate | C22H27N3O6S | 详情 | 详情 |