Itasetron, DAU6215CL, U-98079A, DAU-6215, -Drug Synthesis Database

【结构式】

【药物名称】Itasetron, DAU6215CL, U-98079A, DAU-6215

【化学名称】N-(endo-8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide
　　　　　　2-Oxo-N-(1alphaH,5alphaH-tropan-3alpha-yl)-1-benzimidazoline-1-carboxamide

【CA登记号】123258-84-4, 127618-28-4 (monoHCl)

【分子式】C₁₆H₂₀N₄O₂

【分子量】300.3634

【开发单位】Boehringer Ingelheim (Originator), De Angeli (Originator), Pfizer (Licensee)

【药理作用】Nausea and Vomiting, Treatment of, NEUROLOGIC DRUGS, 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 then condensed with endo-8-methyl-8-azabicyclo[3,2,1]octan-3-amine (IV) 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.

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

合成路线2

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

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.; 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.
【3】 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
(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)	32271	iodomethyl (5R)-3,3-dimethyl-4,4,7-trioxo-4lambda(6)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate		C₉H₁₂INO₅S	详情	详情
(VI)	42927	N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-N'-(2-nitrophenyl)urea		C₁₅H₂₀N₄O₃	详情	详情
(VII)	42928	N-(2-aminophenyl)-N'-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]urea		C₁₅H₂₂N₄O	详情	详情
(VIII)	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(IX)	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