【结 构 式】 |
【分子编号】25356 【品名】(1R)-1-[3-[2-(tert-butoxy)-2-oxoethoxy]phenyl]-3-(3,4-dimethoxyphenyl)propyl (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]-2-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C42H55NO11 【 分 子 量 】749.89884 【元素组成】C 67.27% H 7.39% N 1.87% O 23.47% |
合成路线1
该中间体在本合成路线中的序号:(XVI)3,4,5-Trimethoxyphenylacetic acid (IX) was alkylated with ethyl iodide in the presence of two equivalents of sodium bis(trimethylsilyl)amide to afford racemic trimethoxyphenylbutyric acid (X). After conversion to the corresponding acid chloride with SOCl2, condensation with (R)-4-benzyl-2-oxazolidinone (XI) in the presence of n-butyllithium gave N-acyloxazolidinone (XII) as a diastereomeric mixture that was separated by column chromatography. The required diastereoisomer was then hydrolyzed with lithium peroxide to provide (S)-2-(3,4,5-trimethoxyphenyl)butyric acid (XIII). Subsequent coupling of (XIII) with methyl (S)-pipecolate (XIV) employing 2-chloro-1-methylpyridinium iodide, followed by ester hydrolysis with LiOH, provided amide (XV). Further DCC-promoted coupling of (XV) to alcohol (VIII) provided (XVI). After acid cleavage of the tert-butyl ester, the resulting carboxylic acid was finally coupled to etylenediamine (XVII) in the presence of 1-benzotriazolyloxy tris(dimethylamino)phosphonium hexafluorophosphate to yield the title compound.
【1】 Yang, W.; Guo, T.; Keenan, T.P.; Laborde, E.; Holt, D.A. (Ariad Pharmaceuticals Inc.); Synthetic derivs. of rapamycin as multimerizing agents for chimeric proteins with immunophilin-derived domains. JP 2000505475; WO 9731898 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIII) | 25348 | tert-butyl 2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy]acetate | C23H30O6 | 详情 | 详情 | |
(IX) | 25349 | 2-(3,4,5-trimethoxyphenyl)acetic acid | 937-52-0 | C11H14O5 | 详情 | 详情 |
(X) | 25350 | 2-(3,4,5-trimethoxyphenyl)butyric acid | C13H18O5 | 详情 | 详情 | |
(XI) | 25351 | (4R)-4-benzyl-1,3-oxazolidin-2-one; (R)-(+)-4-benzyl-2-oxazolidinone | 102029-44-7 | C10H11NO2 | 详情 | 详情 |
(XII) | 25352 | (4R)-4-benzyl-3-[2-(3,4,5-trimethoxyphenyl)butanoyl]-1,3-oxazolidin-2-one | C23H27NO6 | 详情 | 详情 | |
(XIII) | 25353 | (2S)-2-(3,4,5-trimethoxyphenyl)butyric acid | C13H18O5 | 详情 | 详情 | |
(XIV) | 25354 | methyl (2S)-2-piperidinecarboxylate | C7H13NO2 | 详情 | 详情 | |
(XV) | 25355 | (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]-2-piperidinecarboxylic acid | C19H27NO6 | 详情 | 详情 | |
(XVI) | 25356 | (1R)-1-[3-[2-(tert-butoxy)-2-oxoethoxy]phenyl]-3-(3,4-dimethoxyphenyl)propyl (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]-2-piperidinecarboxylate | C42H55NO11 | 详情 | 详情 | |
(XVII) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine;1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |