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【结 构 式】 
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【分子编号】26601 【品名】2-[5-[([2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)methyl]-4-methyl-1H-imidazol-1-yl]acetic acid 【CA登记号】 |
【 分 子 式 】C22H25N5O6S 【 分 子 量 】487.5366 【元素组成】C 54.2% H 5.17% N 14.36% O 19.69% S 6.58% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The condensation of 5-(hydroxymethyl)-4-methyl-1H-imidazole (I) with tert-butyl bromoacetate (II) by means of K2CO3 in DMF gives the imidazolylacetic ester (III), which is treated with diphenylphosphoryl azide and DBU in DMF yielding the azidomethyl compound (IV). The reduction of (IV) with H2 over Pd/C in ethyl acetate affords the aminomethyl compound (V), which is acylated with 2-[3-(benzylsulfonamido)-6-methyl-2-oxo-1,2-dihydropyridin-1-yl]acetic acid (VI) by means of EDC and HOBT in DMF providing the carboxamide (VII). Elimination of the tert-butyl group of (VII) with HCl in ethyl acetate gives the free carboxylic acid (VIII), which is finally amidated with tert-butylamine by means of EDC and HOBT in DMF.
| 【1】 Naylor-Olsen, A.M.; Newton, C.L.; Isaacs, R.C.A.; Dorsey, B.D. (Merck & Co., Inc.); Thrombin inhibitors. EP 0969840; US 5932606; WO 9842342 . |
| 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) | 26595 | (4-methyl-1H-imidazol-5-yl)methanol | 38585-62-5 | C5H8N2O | 详情 | 详情 |
| (II) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (III) | 26596 | tert-butyl 2-[5-(hydroxymethyl)-4-methyl-1H-imidazol-1-yl]acetate | C11H18N2O3 | 详情 | 详情 | |
| (IV) | 26597 | tert-butyl 2-[5-(azidomethyl)-4-methyl-1H-imidazol-1-yl]acetate | C11H17N5O2 | 详情 | 详情 | |
| (V) | 26598 | tert-butyl 2-[5-(aminomethyl)-4-methyl-1H-imidazol-1-yl]acetate | C11H19N3O2 | 详情 | 详情 | |
| (VI) | 26599 | 2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetic acid | C15H16N2O5S | 详情 | 详情 | |
| (VII) | 26600 | tert-butyl 2-[5-[([2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)methyl]-4-methyl-1H-imidazol-1-yl]acetate | C26H33N5O6S | 详情 | 详情 | |
| (VIII) | 26601 | 2-[5-[([2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)methyl]-4-methyl-1H-imidazol-1-yl]acetic acid | C22H25N5O6S | 详情 | 详情 |