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【结 构 式】 
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【分子编号】27768 【品名】(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol 【CA登记号】120-29-6 |
【 分 子 式 】C8H15NO 【 分 子 量 】141.21324 【元素组成】C 68.04% H 10.71% N 9.92% O 11.33% |
合成路线1
该中间体在本合成路线中的序号：(I)By reaction of tropine (I) with 3,5-dichlorobenzoyl chloride (II) at 140 C.
| 【1】 Fozard, J.R.; Gittos, M.W. (Aventis Pharma SA); Treatment og migraine with substituted tropyl benzoate derivatives. EP 0067770; JP 58000978 . |
| 【2】 Pento, J.T.; Castaner, J.; Serradell, M.N.; MDL-72222. Drugs Fut 1985, 10, 10, 820. |
合成路线2
该中间体在本合成路线中的序号：(II)By condensation of indole 3-carbonyl chloride (I) with endo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol (II) by means of butyllithium in THF, or Na2CO3 in the same solvent.
| 【1】 Donatsch, P.; Engel, G.; Stadler, P.; Richardson, B.P.; Hügi, B. (Novartis AG; Novartis Deutschland GmbH); Pharmaceutically useful heterocyclic and carbocyclic acid esters and amides of alkylene bridged piperidines. CH 669792; CH 669954; DE 3322574; GB 2166726; GB 2166727; GB 2166728; US 4789673 . |
| 【2】 Castaner, J.; Serradell, M.N.; ICS-205930. Drugs Fut 1986, 11, 2, 106. |
合成路线3
该中间体在本合成路线中的序号：(I)The esterification of endo-8-methyl-8-azabicyclo[3,2,1]octan-3-ol (I) with trichloromethyl chloroformate (II) in acetonitrile gives the corresponding chloroformate (III), which is condensed with 5-methoxy-2-nitroaniline (IV) in pyridine, yielding the carbamate (V). The hydrogenation of the nitro group of (V) with H2 over Pd/C in methanol affords the expected amino derivative (VI). Finally, this compound is cyclized with trichloromethyl chloroformate (II) and Et3N in THF.
| 【1】 Turconi, M.; Schiantarelli, P.; Borsini, F.; Rizzi, C.A.; Ladinsky, H.; Donetti, A.; Azabicycloalkyl benzimidazolones: Interaction with serotonergic 5-HT3 and 5-HT4 receptors and potential therapeutic implications. Drugs Fut 1991, 16, 11, 1011. |
| 【2】 Turconi, M.; et al.; Synthesis of a new class of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives as highly potent 5-HT3 receptor antagonists. J Med Chem 1990, 33, 8, 2101. |
| 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) | 27768 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol | 120-29-6 | C8H15NO | 详情 | 详情 |
| (II) | 42918 | Chloroformic acid trichloromethyl ester; di-Phosgene; Chloroformic Acid, Trichloromethyl Ester; Trichloromethyl chloroformate; Diphosgene | 503-38-8 | C2Cl4O2 | 详情 | 详情 |
| (III) | 42919 | (1R,5S)-3-[(chlorocarbonyl)oxy]-8-methyl-8-azabicyclo[3.2.1]octane | C9H14ClNO2 | 详情 | 详情 | |
| (IV) | 42920 | 5-methoxy-2-nitrophenylamine; 5-methoxy-2-nitroaniline | 16133-49-6 | C7H8N2O3 | 详情 | 详情 |
| (V) | 42921 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 5-methoxy-2-nitrophenylcarbamate | C16H21N3O5 | 详情 | 详情 | |
| (VI) | 42922 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 2-amino-5-methoxyphenylcarbamate | C16H23N3O3 | 详情 | 详情 |