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【结 构 式】 
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【分子编号】44167 【品名】methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-(1H-indol-3-yl)-2-methylpropanoate 【CA登记号】 |
【 分 子 式 】C21H22N2O4 【 分 子 量 】366.41676 【元素组成】C 68.84% H 6.05% N 7.65% O 17.47% |
合成路线1
该中间体在本合成路线中的序号：(III)Condensation of alpha-methyl tryptophan methyl ester (I) with benzylchloroformate (II) in the presence of Et3N in THF yields urethane (III), which is hydrolyzed with LiOH in THF/MeOH/H2O and then activated with DCCI and pentafluorophenol (IV) to furnish ester (V). Treatment of (V) with alpha-methyl-benzylamine (VI) gives derivative (VII), which is then debenzylated by hydrogenation over Pd(OH)2 in EtOH to afford (VIII). Finally, amine (VIII) reacts in DMF with DMAP and carbonate (IX), which has been previously prepared from 2-benzofuranylmethanol (X), 4-nitrophenylchloroformate (XI) and pyridine in CH2Cl2.
| 【1】 Boyle, S.; et al.; Rational design of high affinity tachykinin NK1 receptor antagonists. Bioorg Med Chem 1994, 2, 5, 357. |
| 【2】 Horwell, D.C.; Howson, W.; Rees, D.C.; Roberts, E.; Pritchard, M.C. (Pfizer Inc.); Tachykinin antagonists. EP 0655055; EP 1000930; US 5594022; WO 9404494 . |
| 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) | 44166 | methyl (2R)-2-amino-3-(1H-indol-3-yl)-2-methylpropanoate | C13H16N2O2 | 详情 | 详情 | |
| (II) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (III) | 44167 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-(1H-indol-3-yl)-2-methylpropanoate | C21H22N2O4 | 详情 | 详情 | |
| (IV) | 22662 | 2,3,4,5,6-pentafluorophenol | 771-61-9 | C6HF5O | 详情 | 详情 |
| (V) | 44168 | 2,3,4,5,6-pentafluorophenyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-(1H-indol-3-yl)-2-methylpropanoate | C26H19F5N2O4 | 详情 | 详情 | |
| (VI) | 20042 | (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine | C8H11N | 详情 | 详情 | |
| (VII) | 44169 | benzyl (1R)-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[(1S)-1-phenylethyl]amino]ethylcarbamate | C28H29N3O3 | 详情 | 详情 | |
| (VIII) | 44170 | (2R)-2-amino-3-(1H-indol-3-yl)-2-methyl-N-[(1S)-1-phenylethyl]propanamide | C20H23N3O | 详情 | 详情 | |
| (IX) | 44171 | 1-benzofuran-2-ylmethyl 4-nitrophenyl carbonate | C16H11NO6 | 详情 | 详情 | |
| (X) | 38335 | 1-benzofuran-2-ylmethanol | C9H8O2 | 详情 | 详情 | |
| (XI) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |