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【结 构 式】 
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【分子编号】25283 【品名】(2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-chlorophenyl)propionic acid 【CA登记号】 |
【 分 子 式 】C14H18ClNO4 【 分 子 量 】299.75396 【元素组成】C 56.1% H 6.05% Cl 11.83% N 4.67% O 21.35% |
合成路线1
该中间体在本合成路线中的序号：(IV)Alkylation of 3-phenylpropylamine (I) with methyl bromoacetate (II) provided secondary amine (III), which was coupled with N-Boc-(2-chlorophenyl)alanine (IV) using diisopropyl carbodiimide (DIC) and 7-hydroxy azabenzotriazole (HOAt). After deprotection of the Boc group from the resulting amide (V) with trifluoroacetic acid, cyclization in the presence of Et3N in refluxing MeOH funished piperazinedione (VI). The amide N of (VI) was alkylated with tert-butyl bromoacetate, and the tert-butyl group was then removed using trifluoroacetic acid to provide piperazineacetic acid (VII). This was then coupled to protected amino acid (VIII) by means of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and HOAt to give (IX). Finally, the 2,2,5,7,8-pentamethylchroman-6-sulfonyl protecting group of (IX) was removed with trifluoroacetic acid to furnish the target compound.
| 【1】 Cody, W.L.; et al.; The discovery of potent and selective peptidomimetic inhibitors of thrombin. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 077. |
| 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) | 18791 | 3-phenylpropylamine; 3-phenyl-1-propanamine | 2038-57-5 | C9H13N | 详情 | 详情 |
| (II) | 12309 | methyl 2-bromoacetate; methyl bromoacetate | 96-32-2 | C3H5BrO2 | 详情 | 详情 |
| (III) | 25282 | methyl 2-[(3-phenylpropyl)amino]acetate | C12H17NO2 | 详情 | 详情 | |
| (IV) | 25283 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-chlorophenyl)propionic acid | C14H18ClNO4 | 详情 | 详情 | |
| (V) | 25284 | methyl 2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-chlorophenyl)propanoyl](3-phenylpropyl)amino]acetate | C26H33ClN2O5 | 详情 | 详情 | |
| (VI) | 25285 | (3R)-3-(2-chlorobenzyl)-1-(3-phenylpropyl)-2,5-piperazinedione | C20H21ClN2O2 | 详情 | 详情 | |
| (VII) | 25286 | 2-[(2R)-2-(2-chlorobenzyl)-3,6-dioxo-4-(3-phenylpropyl)piperazinyl]acetic acid | C22H23ClN2O4 | 详情 | 详情 | |
| (VIII) | 25287 | N-[[3-[(2S)-2-amino-3-oxo-3-(1,3-thiazol-2-yl)propyl]-1-piperidinyl](imino)methyl]-2,2,5,7,8-pentamethyl-6-chromanesulfonamide | C26H37N5O4S2 | 详情 | 详情 | |
| (IX) | 25288 | 2-[(2R)-2-(2-chlorobenzyl)-3,6-dioxo-4-(3-phenylpropyl)piperazinyl]-N-[(1S)-1-[[1-(imino[[(2,2,5,7,8-pentamethyl-3,4-dihydro-2H-chromen-6-yl)sulfonyl]amino]methyl)-3-piperidinyl]methyl]-2-oxo-2-(1,3-thiazol-2-yl)ethyl]acetamide | C48H58ClN7O7S2 | 详情 | 详情 |