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【结 构 式】 
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【药物名称】BTS-71091 【化学名称】5-(4-Chlorophenyl)-1-azaspiro[5.5]undec-4-ene hydrochloride 【CA登记号】 【 分 子 式 】C16H21Cl2N 【 分 子 量 】298.25847 |
【开发单位】Abbott (Originator) 【药理作用】Antiobesity Drugs, METABOLIC DRUGS, Treatment of Nutritional Disorders, 5-HT Reuptake Inhibitors, Dopamine Reuptake Inhibitors, Norepinephrine Reuptake Inhibitors |
合成路线1
Fischer esterification of 1-aminocyclohexanecarboxylic acid (I) provided the ethyl ester (II), which was alkylated with ethyl 4-bromobutyrate (III) in the presence of K2CO3 at 100 C to give aminodiester (IV). Dieckmann cyclization of (IV) using NaOEt afforded the azaspiro ketoester (V), which was decarboxylated under acidic conditions to yield ketone (VI). Addition of 4-chlorophenylmagnesium bromide (VII) to (VI) produced the tertiary acohol (VIII). This was dehydrated with concentrated H2SO4 to give the corresponding olefin as the sulfate salt, which was further treated with NaOH and then with HCl to furnish the corresponding hydrochloride.
| 【1】 Harris, P.J.; Kerrigan, F. (The Boots Company plc); Aza spiro alkanes derivs. as therapeutic agents. EP 0667860; JP 1996502985; US 5610161; WO 9411346 . |
| 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) | 31282 | 1-aminocyclohexanecarboxylic acid | 2756-85-6 | C7H13NO2 | 详情 | 详情 |
| (II) | 31283 | ethyl 1-aminocyclohexanecarboxylate | C9H17NO2 | 详情 | 详情 | |
| (III) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (IV) | 31284 | ethyl 1-[(4-ethoxy-4-oxobutyl)amino]cyclohexanecarboxylate | C15H27NO4 | 详情 | 详情 | |
| (V) | 31285 | ethyl 5-oxo-1-azaspiro[5.5]undecane-4-carboxylate | C13H21NO3 | 详情 | 详情 | |
| (VI) | 31286 | 1-azaspiro[5.5]undecan-5-one | C10H17NO | 详情 | 详情 | |
| (VII) | 25127 | bromo(4-chlorophenyl)magnesium | 873-77-8 | C6H4BrClMg | 详情 | 详情 |
| (VIII) | 31287 | 5-(4-chlorophenyl)-1-azaspiro[5.5]undecan-5-ol | C16H22ClNO | 详情 | 详情 |