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【结 构 式】 
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【分子编号】23580 【品名】1-cyclopentyl-2-[[(1S,2S,3S,5R)-2-(2-hydroxyethyl)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]amino]-2-oxoethyl pivalate 【CA登记号】 |
【 分 子 式 】C23H39NO4 【 分 子 量 】393.567 【元素组成】C 70.19% H 9.99% N 3.56% O 16.26% |
合成路线1
该中间体在本合成路线中的序号：(XII)1) The condensation of (IX) with 2-cyclopentyl-2-(pivaloyloxy)acetyl chloride (X) in dichloromethane gives the amide (XI), which is deprotected with p-toluenesulfonie acid in methanol to yield N-(10-hydroxymethylpinan-3-yl)-2-cyclopentyl-2-(pivaloyloxy)acetamide (XII). The oxidation of (XII) with SO3 - pyridine in DMSO affords the aldehyde (XIII), which is submitted to a Wittig condensation with 4-carboxybutyltriphenylphosphonium bromide (XIV) by means ot NaH in DMSO to give the heptenoic acid derivative (XV). The deprotection of (XV) with NaOH yields the racemic mixture (at the 1,5-hydroxy substituent) (XVI), which is finally resolved into its two diastereomers by methylation with diazomethane, column chromatography (silica gel hexane) and hydrolysis with NaOH in methanol.
| 【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 | |
| (XI) | 23579 | 1-cyclopentyl-2-([(1S,2S,3S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]hept-3-yl]amino)-2-oxoethyl pivalate | C29H49NO5 | 详情 | 详情 | |
| (XII) | 23580 | 1-cyclopentyl-2-[[(1S,2S,3S,5R)-2-(2-hydroxyethyl)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]amino]-2-oxoethyl pivalate | C23H39NO4 | 详情 | 详情 | |
| (XIII) | 23581 | 1-cyclopentyl-2-[[(1S,2S,3S,5R)-6,6-dimethyl-2-(2-oxoethyl)bicyclo[3.1.1]hept-3-yl]amino]-2-oxoethyl pivalate | C23H37NO4 | 详情 | 详情 | |
| (XIV) | 23582 | (4-carboxybutyl)(triphenyl)phosphonium | C23H24O2P | 详情 | 详情 | |
| (XV) | 23583 | (Z)-7-[(1S,2S,3S,5R)-3-([2-cyclopentyl-2-[(2,2-dimethylpropanoyl)oxy]acetyl]amino)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]-5-heptenoic acid | C28H45NO5 | 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 |