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【结 构 式】 
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【分子编号】55152 【品名】di(tert-butyl) (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-hydroxy-2-methylpentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate 【CA登记号】 |
【 分 子 式 】C25H44N2O6 【 分 子 量 】468.63424 【元素组成】C 64.07% H 9.46% N 5.98% O 20.48% |
合成路线1
该中间体在本合成路线中的序号：(XX)Oxidation of alcohol (XVIII) employing the Dess-Martin periodinane reagent furnished ketone (XIX). Subsequent addition of methylmagnesium bromide to ketone (XIX) gave rise to a mixture of diastereoisomeric carbinols from which alcohol (XX) was isolated as the major isomer. The methyl ether (XXI) was prepared by alkylation of the sodium alkoxide of (XX) with iodomethane in THF. Trifluoroacetic acid-promoted cleavage of the tert-butyl ester and N-Boc protecting groups provided the title compound in the racemic form (+/-)-(XXII). The ethyl ester prepared by esterification of (+/-)-(XXII) with EtOH and SOCl2 was then resolved using chiral HPLC. The desired enantiomer (XXIII) was finally hydrolyzed with LiOH to the title levo carboxylic acid.
| 【1】 Inhibitors of neuraminidases. WO 0128996 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 55150 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2R)-1-(acetylamino)-2-hydroxypentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C24H42N2O6 | 详情 | 详情 | |
| (XIX) | 55151 | di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-oxopentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C24H40N2O6 | 详情 | 详情 | |
| (XX) | 55152 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-hydroxy-2-methylpentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C25H44N2O6 | 详情 | 详情 | |
| (XXI) | 55153 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C26H46N2O6 | 详情 | 详情 | |
| (XXII) | 55154 | (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(Z)-1-propenyl]-2-pyrrolidinecarboxylic acid | C17H30N2O4 | 详情 | 详情 | |
| (XXIII) | 55166 | ethyl (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(Z)-1-propenyl]-2-pyrrolidinecarboxylate | C19H34N2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XX)Oxidation of alcohol (XVIII) employing the Dess-Martin periodinane reagent furnished ketone (XIX). Subsequent addition of MeMgBr to ketone (XIX) gave rise to a mixture of diastereoisomeric carbinols from which alcohol (XX) was isolated as the major isomer. The methyl ether (XXI) was prepared by alkylation of the sodium alkoxide of (XX) with iodomethane in THF. Trifluoroacetic acid-promoted cleavage of the tert-butyl ester and N-Boc protecting groups of (XXI) provided the carboxylic acid (XXII). The title ester enantiomer was then obtained by esterification of racemic (XXII) with EtOH and SOCl2, followed by resolution using chiral HPLC.
| 【1】 Inhibitors of neuraminidases. WO 0128996 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 55150 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2R)-1-(acetylamino)-2-hydroxypentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C24H42N2O6 | 详情 | 详情 | |
| (XIX) | 55151 | di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-oxopentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C24H40N2O6 | 详情 | 详情 | |
| (XX) | 55152 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-hydroxy-2-methylpentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C25H44N2O6 | 详情 | 详情 | |
| (XXI) | 55153 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C26H46N2O6 | 详情 | 详情 | |
| (XXII) | 55154 | (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(Z)-1-propenyl]-2-pyrrolidinecarboxylic acid | C17H30N2O4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XX)Oxidation of alcohol (XVIII) employing the Dess-Martin periodinane reagent furnished ketone (XIX). Subsequent addition of methylmagnesium bromide to ketone (XIX) gave rise to a mixture of diastereoisomeric carbinols from which alcohol (XX) was isolated as the major isomer. The methyl ether (XXI) was prepared by alkylation of the sodium alkoxide of (XX) with iodomethane in THF. Trifluoroacetic acid-promoted cleavage of the tert-butyl ester and N-Boc protecting groups of (XXI) provided the carboxylic acid (XXII). The title isopropyl ester was then obtained by esterification of acid (XXII) with 2-propanol and SOCl2.
| 【1】 Inhibitors of neuraminidases. WO 0128996 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 55150 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2R)-1-(acetylamino)-2-hydroxypentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C24H42N2O6 | 详情 | 详情 | |
| (XIX) | 55151 | di(tert-butyl) (2R,4S,5R)-5-[(1R)-1-(acetylamino)-2-oxopentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C24H40N2O6 | 详情 | 详情 | |
| (XX) | 55152 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-hydroxy-2-methylpentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C25H44N2O6 | 详情 | 详情 | |
| (XXI) | 55153 | di(tert-butyl) (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(Z)-1-propenyl]-1,2-pyrrolidinedicarboxylate | C26H46N2O6 | 详情 | 详情 | |
| (XXII) | 55154 | (2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(Z)-1-propenyl]-2-pyrrolidinecarboxylic acid | C17H30N2O4 | 详情 | 详情 |