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【结 构 式】 
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【分子编号】46945 【品名】methyl 4-[4-(5-methyl-1-trityl-1H-imidazol-4-yl)-1-piperidinyl]-3-nitrobenzoate 【CA登记号】 |
【 分 子 式 】C36H34N4O4 【 分 子 量 】586.69052 【元素组成】C 73.7% H 5.84% N 9.55% O 10.91% |
合成路线1
该中间体在本合成路线中的序号：(V)Esterification of 4-fluoro-3-nitrobenzoic acid (I) with MeOH in the presence of SOCl2 provided the methyl ester (II). Subsequent displacement of the fluoro group with the imidazolyl piperidine (III) gave adduct (IV), which was further protected as the N-trityl derivative (V) using triphenylmethyl chloride and N-methylmorpholine. Catalytic hydrogenation of the nitro group of (V) over Raney-Ni produced aniline (VI), which was acylated with cyclopropanecarbonyl chloride (VII) to furnish amide (VIII). After basic hydrolysis of the methyl ester group of (VIII), the resultant carboxylic acid (IX) was coupled with N,N-dimethyl ethanediamine (X) using PyBOP to yield amide (XI). Finally, acidic treatment of (XI) with HOAc removed the N-trityl protecting group.
| 【1】 Hoornaert, C.; Rouannet, V.; Dellac, G.; Daumas, M.; Adler, M.-A.; Cremer, G. (Sanofi-Synthelabo); 4-[(1H-Imidazol-4-yl)piperidin-1-yl]anilide derivs., their preparation and application in therapy. EP 0991639; WO 9900379 . |
| 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) | 46937 | 4-fluoro-3-nitrobenzoic acid | 453-71-4 | C7H4FNO4 | 详情 | 详情 |
| (II) | 46938 | methyl 4-fluoro-3-nitrobenzoate | C8H6FNO4 | 详情 | 详情 | |
| (III) | 46939 | 4-(5-methyl-1H-imidazol-4-yl)piperidine | C9H15N3 | 详情 | 详情 | |
| (IV) | 46940 | methyl 4-[4-(5-methyl-1H-imidazol-4-yl)-1-piperidinyl]-3-nitrobenzoate | C17H20N4O4 | 详情 | 详情 | |
| (V) | 46945 | methyl 4-[4-(5-methyl-1-trityl-1H-imidazol-4-yl)-1-piperidinyl]-3-nitrobenzoate | C36H34N4O4 | 详情 | 详情 | |
| (VI) | 46941 | methyl 3-amino-4-[4-(5-methyl-1-trityl-1H-imidazol-4-yl)-1-piperidinyl]benzoate | C36H36N4O2 | 详情 | 详情 | |
| (VII) | 14061 | Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride | 4023-34-1 | C4H5ClO | 详情 | 详情 |
| (VIII) | 46942 | methyl 3-[(cyclopropylcarbonyl)amino]-4-[4-(5-methyl-1-trityl-1H-imidazol-4-yl)-1-piperidinyl]benzoate | C40H40N4O3 | 详情 | 详情 | |
| (IX) | 46943 | 3-[(cyclopropylcarbonyl)amino]-4-[4-(5-methyl-1-trityl-1H-imidazol-4-yl)-1-piperidinyl]benzoic acid | C39H38N4O3 | 详情 | 详情 | |
| (X) | 14881 | N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine | 108-00-9 | C4H12N2 | 详情 | 详情 |
| (XI) | 46944 | 3-[(cyclopropylcarbonyl)amino]-N-[2-(dimethylamino)ethyl]-4-[4-(5-methyl-1-trityl-1H-imidazol-4-yl)-1-piperidinyl]benzamide | C43H48N6O2 | 详情 | 详情 |