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【结 构 式】 
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【分子编号】41808 【品名】(2S)-2-cyclopentyl-2-[4-[(2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl)methyl]phenyl]ethanoic acid 【CA登记号】 |
【 分 子 式 】C27H28N2O2 【 分 子 量 】412.5316 【元素组成】C 78.61% H 6.84% N 6.79% O 7.76% |
合成路线1
该中间体在本合成路线中的序号：(XX)Esterification of 2-(4-methylphenyl)acetic acid (XI) with L-menthol (XV) by means of MsOH in refluxing toluene gives the ester (XVI), which is diastereoselectively condensed with cyclopentyl bromide (XIII) by means of t-BuOK in DMF, affording 2(S)-cyclopentyl-2-(4-methylphenyl)acetic acid L-menthyl ester (XVII). Bromination of (XVII) with 1,3-dibromo-5,5-dimethylhydantoin (DBMH) in hot chlorobenzene gives the chiral benzyl bromide (XVIII), which is condensed with the already described alpha-carboline (VI) by means of t-BuOK in DMF to yield the adduct (XIX). Hydrolysis of (XIX) with HBr in formic acid affords the chiral cyclopentylacetic acid (XX), which is treated with SOCl2 in refluxing CH2Cl2 to provide the corresponding acyl chloride (XXI). Finally, this compound is condensed with (R)-2-hydroxy-1-phenylethylamine (X) by means of TEA in hot toluene.
| 【1】 Castañer, J.; Silvestre, J.S.; Sorbera, L.A.; Martín, L.; Implitapide. Drugs Fut 2000, 25, 11, 1138. |
| 【2】 Fey, P.; Naab, P.; Lenfers, J.-B.; Van Laak, K. (Bayer AG); Process for the preparation of enantiomerically pure cycloalkano-indol -and azaindol -and pyrimido[1,2a]indolcarboxycyclic acids and their activated derivs.. CA 2201435; DE 19613549; EP 0799829; JP 1998045759; US 5952498 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 41797 | 2,4-dimethyl-9H-pyrido[2,3-b]indole | C13H12N2 | 详情 | 详情 | |
| (X) | 14376 | (2R)-2-amino-2-phenyl-1-ethanol; (R)-(-)-2-phenylglycinol; (R)-2-amino-2-phenyl-1-ethanol | 56613-80-0 | C8H11NO | 详情 | 详情 |
| (XI) | 28316 | 2-(4-methylphenyl)acetic acid | 622-47-9 | C9H10O2 | 详情 | 详情 |
| (XIII) | 10792 | Butanoyl chloride; Butyryl chloride | 141-75-3 | C4H7ClO | 详情 | 详情 |
| (XV) | 41803 | (1R,2S,5R)-2-isopropyl-5-methylcyclohexanol; L-menthol | 2216-51-5 | C10H20O | 详情 | 详情 |
| (XVI) | 41804 | (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-(4-methylphenyl)acetate | C19H28O2 | 详情 | 详情 | |
| (XVII) | 41805 | (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2S)-2-cyclopentyl-2-(4-methylphenyl)ethanoate | C24H36O2 | 详情 | 详情 | |
| (XVIII) | 41806 | (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2S)-2-[4-(bromomethyl)phenyl]-2-cyclopentylethanoate | C24H35BrO2 | 详情 | 详情 | |
| (XIX) | 41807 | (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2S)-2-cyclopentyl-2-[4-[(2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl)methyl]phenyl]ethanoate | C37H46N2O2 | 详情 | 详情 | |
| (XX) | 41808 | (2S)-2-cyclopentyl-2-[4-[(2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl)methyl]phenyl]ethanoic acid | C27H28N2O2 | 详情 | 详情 | |
| (XXI) | 41809 | (2S)-2-cyclopentyl-2-[4-[(2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl)methyl]phenyl]ethanoyl chloride | C27H27ClN2O | 详情 | 详情 |