【结 构 式】 |
【分子编号】17119 【品名】(3R,5S)-5-[(R)-hydroxy[(3R)-1-methyltetrahydro-1H-pyrrol-3-yl]methyl]-1-methyltetrahydro-1H-pyrrol-3-ol 【CA登记号】 |
【 分 子 式 】C11H22N2O2 【 分 子 量 】214.30796 【元素组成】C 61.65% H 10.35% N 13.07% O 14.93% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The thiol (II) has been obtained as follows: The aldehyde (V), which is synthesized from trans-4-hydroxy-L-proline in several steps (3), reacts with the lithium enolate of the pyrrolidone (IV) to afford the alcohol (VI) and its diastereomeric isomers. After purification on a silica gel column, reduction of (VI) by borane-dimethylsulfide in refluxing THF gives (VII). Removal of the amino protecting groups of (VII) by TFA, followed by reprotection with PNZ groups and then removal of the tert-butyldimethylsilyl group with Bu4NF gives the diol (VIII). Selective mesylation of (VIII), followed by reaction with potassium thioacetate, gives (IX), which is treated with aqueous 1 N NaOH in methanol to afford the thiol (II).
【1】 Sato, N.; Ohba, F.; ER-35786. Drugs Fut 1996, 21, 4, 361. |
【2】 Nakagawa, S.; Ohtake, N.; Nakano, F.; Yamada, K.; Ushijima, R.; Murase, S.; Fukatsu, H. (Banyu Pharmaceutical Co., Ltd.); 2-(Substd. pyrrolidinylthio)carbapenem derivs. EP 0449191; JP 1992321688; US 5373002; US 5374720; US 5438054; WO 9114687 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II) | 17113 | (R)-[(2S,4S)-1-methyl-4-sulfanyltetrahydro-1H-pyrrol-2-yl][(3R)-1-methyltetrahydro-1H-pyrrol-3-yl]methanol | C11H22N2OS | 详情 | 详情 | |
(IV) | 17115 | 1-Methyl-2-pyrrolidinone | 872-50-4 | C5H9NO | 详情 | 详情 |
(V) | 17116 | (2S,4R)-4-hydroxy-1-methyltetrahydro-1H-pyrrole-2-carbaldehyde | C6H11NO2 | 详情 | 详情 | |
(VI) | 17117 | (3S)-3-[(R)-hydroxy[(2S,4R)-4-hydroxy-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-1-methyltetrahydro-2H-pyrrol-2-one | C11H20N2O3 | 详情 | 详情 | |
(VII) | 17118 | (R)-((2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-1-methylpyrrolidinyl)[(3R)-1-methylpyrrolidinyl]methanol | C11H22N2O2 | 详情 | 详情 | |
(VIII) | 17119 | (3R,5S)-5-[(R)-hydroxy[(3R)-1-methyltetrahydro-1H-pyrrol-3-yl]methyl]-1-methyltetrahydro-1H-pyrrol-3-ol | C11H22N2O2 | 详情 | 详情 | |
(IX) | 17120 | S-((3S,5S)-5-[(R)-hydroxy[(3R)-1-methyltetrahydro-1H-pyrrol-3-yl]methyl]-1-methyltetrahydro-1H-pyrrol-3-yl) ethanethioate | C13H24N2O2S | 详情 | 详情 |