N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-N'-(2-nitrophenyl)urea -Drug Synthesis Database

【结构式】

【分子编号】42927

【品名】N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-N'-(2-nitrophenyl)urea

【CA登记号】

【分子式】C₁₅H₂₀N₄O₃

【分子量】304.34896

【元素组成】C 59.2% H 6.62% N 18.41% O 15.77%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VI)

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

合成目标

【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

合成路线2

该中间体在本合成路线中的序号：(VIII)

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 ethyl chloride (VI) and NaH in DMF.

参考文献中间体

合成目标

【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.; 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.
【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)	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)	42926	1-chloroethane	75-00-3	C₂H₅Cl	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

合成路线3

该中间体在本合成路线中的序号：(VIII)

参考文献中间体

合成目标

【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