【结 构 式】 |
【药物名称】 【化学名称】(Piperidin-3-yl)phosphinic acid 【CA登记号】 【 分 子 式 】C5H12NO2P 【 分 子 量 】149.13069 |
【开发单位】Danish University of Pharmaceutical Sci. (Originator) 【药理作用】GABA Reuptake Inhibitors |
合成路线1
The protection of 3-piperidinol (I) with tert-butoxycarbonyl anhydride or benzyloxycarbonyl chloride gives the corresponding protected piperidine (II), which is oxidized with CrO3 and acetic anhydride in pyridine yielding the piperidinone (III). The condensation of (III) with phosphinate (IV) and triethylamine at 100 C affords the alpha-hydroxyphosphinate (V), which is acylated with methoxalyl chloride (VI) and DMAP giving the methoxalyl ester (VII). The reduction of (VII) with tributyl in hydride and AIBN yields the protected phophinate (VIII), which is finally deprotected and hydrolyzed with 6M HCl.
【1】 Stensbol, T.B.; Kehler, J.; Krogsgaard-Larsen, P.; Piperidinyl-3-phosphinic acids as novel uptake inhibitors of the neurotransmitter gamma-aminobutyric acid (GABA). Bioorg Med Chem Lett 1999, 9, 6, 811. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
(IIa) | 26964 | benzyl 3-hydroxy-1-piperidinecarboxylate | C13H17NO3 | 详情 | 详情 | |
(IIb) | 26965 | tert-butyl 3-hydroxy-1-piperidinecarboxylate | C10H19NO3 | 详情 | 详情 | |
(IIIa) | 26966 | benzyl 3-oxo-1-piperidinecarboxylate | C13H15NO3 | 详情 | 详情 | |
(IIIb) | 26967 | 1-N-Boc-3-piperodone; tert-butyl 3-oxo-1-piperidinecarboxylate | 98977-36-7 | C10H17NO3 | 详情 | 详情 |
(Va) | 26969 | benzyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-3-hydroxy-1-piperidinecarboxylate | C20H32NO7P | 详情 | 详情 | |
(Vb) | 26970 | tert-butyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-3-hydroxy-1-piperidinecarboxylate | C17H34NO7P | 详情 | 详情 | |
(VIIa) | 26972 | benzyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-3-[(2-methoxy-2-oxoacetyl)oxy]-1-piperidinecarboxylate | C23H34NO10P | 详情 | 详情 | |
(VIIb) | 26973 | tert-butyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-3-[(2-methoxy-2-oxoacetyl)oxy]-1-piperidinecarboxylate | C20H36NO10P | 详情 | 详情 | |
(VIIIa) | 26974 | benzyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-1-piperidinecarboxylate | C20H32NO6P | 详情 | 详情 | |
(VIIIb) | 26975 | tert-butyl 3-[(diethoxymethyl)(ethoxy)phosphoryl]-1-piperidinecarboxylate | C17H34NO6P | 详情 | 详情 | |
(I) | 24255 | 3-piperidinol | 6859-99-0 | C5H11NO | 详情 | 详情 |
(IV) | 26968 | ethyl diethoxymethylphosphinate | C7H17O4P | 详情 | 详情 | |
(VI) | 26971 | 2-methoxy-2-oxoacetyl chloride | 5781-53-3 | C3H3ClO3 | 详情 | 详情 |