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【结 构 式】 
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【药物名称】 【化学名称】4-[4-[1-[4-(1,3-Benzodioxol-5-ylsulfonyl)phenyl]-1-(1,3-dioxolan-2-yl)methyl]piperidin-1-yl]-1-(propylsulfonyl)piperidine 【CA登记号】 【 分 子 式 】C29H38N2O8S2 【 分 子 量 】606.76281 |
【开发单位】Schering-Plough (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Muscarinic M2 Antagonists |
合成路线1
N-protection of the NH group of (I) with Boc2O and NaOH in Et2O yields derivative (II), which is then condensed with compound (III) by means of NaH in DMF to provide (IV). N-deprotection of (IV) by treatment with TFA in CH2Cl2 followed by reductocondensation with N-Boc-4-piperidone (V) in CH2Cl2 in the presence of Na(OAc)3BH affords compound (VI), which is oxidized with NaBO3.4H2O to provide (VII). Boc removal of (VII) by treatment with TFA in CH2Cl2, followed by reaction of the resulting secondary amine with sulfonyl chloride (VIII) in CH2Cl2 in the presence of Et3N, affords propylsulfonamide derivative (IX). Finally, treatment of (IX) with ethyleneglycol (X) in toluene in the presence of HC(OEt)3 and p-TsOH furnishes the target compound.
| 【1】 Boyle, C.D.; Chackalamannil, S.; Chen, L.-Y.; et al.; Benzylidine ketal derivatives as M2 muscarinic receptor antagonists. Bioorg Med Chem Lett 2000, 10, 24, 2727. |
| 【2】 Chackalamannil, S.; Chen, L.-Y.; Boyle, C.D.; et al.; Benzylidene ketal derivatives as M2 muscarinic receptor antagonists. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 114. |
| 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) | 21497 | (4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine | 56346-57-7 | C12H14FNO | 详情 | 详情 |
| (II) | 45867 | tert-butyl 4-(4-fluorobenzoyl)-1-piperidinecarboxylate | C17H22FNO3 | 详情 | 详情 | |
| (III) | 28620 | 1,3-benzodioxole-5-thiol | C7H6O2S | 详情 | 详情 | |
| (IV) | 45868 | tert-butyl 4-[4-(1,3-benzodioxol-5-ylsulfanyl)benzoyl]-1-piperidinecarboxylate | C24H27NO5S | 详情 | 详情 | |
| (V) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (VI) | 45869 | C29H36N2O5S | 详情 | 详情 | ||
| (VII) | 45870 | C29H36N2O7S | 详情 | 详情 | ||
| (VIII) | 45871 | 1-propanesulfonyl chloride；Propanesulfonylchloride；n-Propylsulphonyl chloride；Propylsulfonyl chloride;n-Propanesulfonyl chloride; | 10147-36-1 | C3H7ClO2S | 详情 | 详情 |
| (IX) | 45872 | C27H34N2O7S2 | 详情 | 详情 | ||
| (X) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |