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【结 构 式】 
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【药物名称】 【化学名称】(3R,4R,5'S)-5'-Methylspiro[1-azabicyclo[2.2.1]octane-3,2'-tetrahydrofuran]-4'-one 【CA登记号】 【 分 子 式 】C10H15NO2 【 分 子 量 】181.23655 |
【开发单位】AstraZeneca (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Muscarinic Agonists |
合成路线1
The Horner-Emmons reaction of 1-azabicyclo[2.2.1]heptan-3-one (I) with triethyl phosphonoacetate (II) gave conjugated ester (III). Subsequent Michael addition of the oxyanion of ethyl (S)-lactate (IV), generated in the presence of NaH in DMF, with concomitant Dieckmann cyclization, produced ketoester (V). Then, hydrolysis and decarboxylation in boiling 1 N HCl, followed by separation of the syn and anti isomers, yielded the title compound.
| 【1】 Wu, E.S.C.; Kover, A.; Semus, S.F.; Synthesis and modeling studies of a potent conformationally rigid muscarinic agonist: 1-Azabicyclo[2.2.1]heptanespirofuranone. J Med Chem 1998, 41, 22, 4181. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 20473 | 1-azabicyclo[2.2.1]heptan-3-one | C6H9NO | 详情 | 详情 | |
| (II) | 20474 | ethyl 2-[(diethoxyphosphino)oxy]acetate | C8H17O5P | 详情 | 详情 | |
| (III) | 20475 | ethyl 2-(1-azabicyclo[2.2.1]hept-3-ylidene)acetate | C10H15NO2 | 详情 | 详情 | |
| (IV) | 16659 | ethyl (2S)-2-hydroxypropanoate; (S)-ethyl lactate | 687-47-8 | C5H10O3 | 详情 | 详情 |
| (V) | 20477 | 5'-Methyl-4'-oxospiro[1-azabicyclo[2,2,1]octane-3(S),2'-tetrahydrofuran]-3'-ylcarboxylic acid ethyl ester | C13H19NO4 | 详情 | 详情 |
Extended Information