DAU-6285, -Drug Synthesis Database

【结构式】

【药物名称】DAU-6285

【化学名称】6-Methoxy-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxylic acid (endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester hydrochloride

【CA登记号】123258-98-0

【分子式】C₁₇H₂₂ClN₃O₄

【分子量】367.83559

【开发单位】De Angeli (Originator)

【药理作用】5-HT4 Antagonists

合成路线1

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.

参考文献中间体

【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

Extended Information