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【结 构 式】 
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【分子编号】23587 【品名】N-[(1S,2S,3S,5R)-6,6-dimethyl-2-(2-oxoethyl)bicyclo[3.1.1]hept-3-yl]-2,2,2-trifluoroacetamide 【CA登记号】 |
【 分 子 式 】C13H18F3NO2 【 分 子 量 】277.2866696 【元素组成】C 56.31% H 6.54% F 20.55% N 5.05% O 11.54% |
合成路线1
该中间体在本合成路线中的序号：(XIX)2) Amine (IX) is acylated with trifluoroacetic anhydride and pyridine in dichloromethane to the amide (XVII), which is hydrolyzed with p-toluenesulfonic acid in methanol yielding the alcohol (XVIII). The oxidation of (XVIII) with anhydrous H2SO4 - pyridine in DMSO triethylamine affords the aldehyde (XIX), which is submitted to a Wittig condensation with 4-carboxybutyltriphenylphosphonium bromide by means of NaH in DMSO giving the heptenoic acid (XX). Methylation of (XX) with diazomethane affords the corresponding methyl ester (XXI), which is deprotected with NaOH yielding the amino ester (XXII). The acylation of (XXII) with the acyl chloride (X) gives the protected amido ester (XXIII), which by partial hydrolysis with NaOH affords the racemic mixture (XVI), already obtained.
| 【1】 Kawasaki, A.; Miyake, H.; Okegawa, T. (Ono Pharmaceutical Co., Ltd.); 13-Aza-14-oxo-TXA2 analogues. AU 8543495; EP 0171146; ES 8704880; ES 8705370; JP 1989151545; US 4792550 . |
| 【2】 Castaner, J.; Prous, J.; ONO-3708. Drugs Fut 1987, 12, 5, 446. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 23577 | (1S,2S,3S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]heptan-3-amine; (1S,2S,3S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]hept-3-ylamine | C17H31NO2 | 详情 | 详情 | |
| (X) | 23578 | 2-chloro-1-cyclopentyl-2-oxoethyl pivalate | C12H19ClO3 | 详情 | 详情 | |
| (XIV) | 23582 | (4-carboxybutyl)(triphenyl)phosphonium | C23H24O2P | 详情 | 详情 | |
| (XVI) | 23584 | (Z)-7-[(1S,2S,3S,5R)-3-[(2-cyclopentyl-2-hydroxyacetyl)amino]-6,6-dimethylbicyclo[3.1.1]hept-2-yl]-5-heptenoic acid | C23H37NO4 | 详情 | 详情 | |
| (XVII) | 23585 | N-[(1S,2S,3S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]hept-3-yl]-2,2,2-trifluoroacetamide | C19H30F3NO3 | 详情 | 详情 | |
| (XVIII) | 23586 | 2,2,2-trifluoro-N-[(1S,2S,3S,5R)-2-(2-hydroxyethyl)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]acetamide | C13H20F3NO2 | 详情 | 详情 | |
| (XIX) | 23587 | N-[(1S,2S,3S,5R)-6,6-dimethyl-2-(2-oxoethyl)bicyclo[3.1.1]hept-3-yl]-2,2,2-trifluoroacetamide | C13H18F3NO2 | 详情 | 详情 | |
| (XX) | 23588 | (Z)-7-[(1S,2S,3S,5R)-6,6-dimethyl-3-[(2,2,2-trifluoroacetyl)amino]bicyclo[3.1.1]hept-2-yl]-5-heptenoic acid | C18H26F3NO3 | 详情 | 详情 | |
| (XXI) | 23589 | (Z)-7-[(1S,2S,5R)-6,6-dimethyl-3-[(2,2,2-trifluoroacetyl)amino]bicyclo[3.1.1]hept-2-yl]-5-heptenoic acid | C18H26F3NO3 | 详情 | 详情 | |
| (XXII) | 23590 | (Z)-7-[(1S,2S,3S,5R)-3-amino-6,6-dimethylbicyclo[3.1.1]hept-2-yl]-5-heptenoic acid | C16H27NO2 | 详情 | 详情 | |
| (XXIII) | 23591 | methyl (Z)-7-[(1S,2S,3S,5R)-3-[(2-cyclopentyl-2-hydroxyacetyl)amino]-6,6-dimethylbicyclo[3.1.1]hept-2-yl]-5-heptenoate | C24H39NO4 | 详情 | 详情 |