BIMU-8, -Drug Synthesis Database

【结构式】

【药物名称】BIMU-8

【化学名称】3-Isopropyl-N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide hydrochloride

【CA登记号】134296-40-5

【分子式】C₁₉H₂₇ClN₄O₂

【分子量】378.90564

【开发单位】De Angeli (Originator)

【药理作用】Gastric Emptying Disorders,Treatment of of, GASTROINTESTINAL DRUGS, Nausea and Vomiting, Treatment of, NEUROLOGIC DRUGS, Prokinetic Agents, 5-HT3 Antagonists, 5-HT4 Agonists

合成路线1 合成路线2

合成路线1

The reaction of 2,3-dihydro-1H-benzimidazol-2-one (I) with trichloromethyl chloroformate (II) in THF gives 2-oxo-2,3-dihydro-1H-benzimidazol-2-ylcarbonyl chloride (III), which is condensed with endo-8-methyl-8-azabicyclo[3,2,1]octan-3-amine (IV) in THF, yielding the corresponding amide (V). Finally, this compound is alkylated with isopropyl bromide (VI) and NaH in DMF.

参考文献中间体

【1】 Turconi, M.; et al.; Azabicycloalkyl benzimidazolone derivatives: A novel class of 5-HT3 receptor antagonists. 199th ACS Natl Meet (April 22 1990, Boston) 1990, Abst MEDI 103.
【2】 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.

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)	42923	1,3-dihydro-2H-benzimidazol-2-one	615-16-7	C₇H₆N₂O	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)	42924	2-oxo-2,3-dihydro-1H-benzimidazole-1-carbonyl chloride		C₈H₅ClN₂O₂	详情	详情
(IV)	19105	(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine; (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-amine		C₈H₁₆N₂	详情	详情
(V)	42925	N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide		C₁₆H₂₀N₄O₂	详情	详情
(VI)	29984	2-chloropropane	75-29-6	C₃H₇Cl	详情	详情

合成路线2

The condensation of 2-nitrophenyl isocyanate (VII) with endo-8-methyl-8-azabicyclo[3,2,1]octan-3-amine (IV) in THF/cyclohexane gives the corresponding 2-nitrophenylurea (VIII), which is reduced with H2 over Pd/C in ethanol to yield the 2-aminophenylurea (IX). The acylation of (IX) with phenyl chloroformate (X) in toluene affords the carbamate (XI), which is cyclized by means of NaOH in ethanol to afford the amide (V). Finally, this compound is alkylated with isopropyl bromide (VI) and NaH in DMF.

参考文献中间体

【1】 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.
【2】 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.
【3】 Turconi, M.; et al.; Azabicycloalkyl benzimidazolone derivatives: A novel class of 5-HT3 receptor antagonists. 199th ACS Natl Meet (April 22 1990, Boston) 1990, Abst MEDI 103.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	19105	(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine; (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-amine		C₈H₁₆N₂	详情	详情
(V)	42925	N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide		C₁₆H₂₀N₄O₂	详情	详情
(VI)	29984	2-chloropropane	75-29-6	C₃H₇Cl	详情	详情
(VII)	32771	1-isocyanato-2-nitrobenzene; 2-nitrophenyl isocyanate	3320-86-3	C₇H₄N₂O₃	详情	详情
(VIII)	42927	N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-N'-(2-nitrophenyl)urea		C₁₅H₂₀N₄O₃	详情	详情
(IX)	42928	N-(2-aminophenyl)-N'-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]urea		C₁₅H₂₂N₄O	详情	详情
(X)	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(XI)	42929	phenyl 2-[([[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]amino]carbonyl)amino]phenylcarbamate		C₂₂H₂₆N₄O₃	详情	详情

Extended Information