ethyl (Z)-3-(4-nitrophenyl)-3-phenyl-2-propenoate -Drug Synthesis Database

【结构式】

【分子编号】59466

【品名】ethyl (Z)-3-(4-nitrophenyl)-3-phenyl-2-propenoate

【CA登记号】

【分子式】C₁₇H₁₅NO₄

【分子量】297.31044

【元素组成】C 68.68% H 5.09% N 4.71% O 21.53%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XI)

Horner-Emmons condensation of 4-nitrobenzophenone (IX) with triethyl phosphonoacetate produced a 2:1 mixture of Z and E nitrophenylcinnamic esters (XI) and (X). Alternatively, the desired Z isomer was obtained in a more favorable 8:1 ratio by condensation of (IX) with ethyl (trimethylsilyl)acetate under Peterson reaction conditions. Ester hydrolysis in the mixture (X) + (XI) with K2CO3 in aqueous methanol gave the corresponding mixture of carboxylic acids (XII). Optionally, the pure Z isomer could be isolated by recrystallization from EtOAc. DCC coupling of piperidine (VIII) with either the pure Z-isomer or the Z/E-mixture of carboxylic acids (XIIa-b) gave rise to the respective Z/E isomeric amides (XIIIa-b). After catalytic hydrogenation of the nitro group of (XIII), the required Z-(4-aminophenyl)cinnamamide isomer (XIV) was isolated by column chromatography. Finally, diazotization of (XIV), followed by coupling of the resultant diazonium salt (XV) to salicylic acid, furnished the title diazo compound.

参考文献中间体

合成目标

【1】 Ferrando, R.; Carceller, E.; Forn, J.; Ramis, J.; Escamilla, I.; Giral, M.; Merlos, M.; Salas, J.; García-Rafanell, J.; Novel azo derivatives prodrugs of 5-aminosalicylic acid and amino derivatives with potent platelet activating factor antagonist activity. J Med Chem 2001, 44, 18, 3001.
【2】 Carceller, E.; Jimenez, P.J.; Salas, J.; Almansa, C.; Bartroli, J.; Merlos, M.; Giral, M.; Balsa, D.; Ferrando, R.; Garcia-Rafanell, J.; Forn, J. (J. Uriach & Cía., SA); Azo derivs. of 5-aminosalicylic acid for treatment of inflammatory bowel disease. EP 0790998; ES 2104513; ES 2106682; JP 1999501939; US 5747477; WO 9709329 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIIa)	59467	(E)-3-(4-nitrophenyl)-3-phenyl-2-propenoic acid		C₁₅H₁₁NO₄	详情	详情
(XIIb)	59468	(Z)-3-(4-nitrophenyl)-3-phenyl-2-propenoic acid		C₁₅H₁₁NO₄	详情	详情
(XIIIa)	59469	(E)-1-{4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl}-3-(4-nitrophenyl)-3-phenyl-2-propen-1-one		C₂₈H₂₇N₅O₃	详情	详情
(XIIIb)	59470	(Z)-1-{4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl}-3-(4-nitrophenyl)-3-phenyl-2-propen-1-one		C₂₈H₂₇N₅O₃	详情	详情
(VIII)	59463	2-methyl-1-(4-piperidinylmethyl)-1H-imidazo[4,5-c]pyridine		C₁₃H₁₈N₄	详情	详情
(IX)	59464	4-Nitrobenzophenone; p-Nitrobenzophenone	1144-74-7	C₁₃H₉NO₃	详情	详情
(X)	59465	ethyl (E)-3-(4-nitrophenyl)-3-phenyl-2-propenoate		C₁₇H₁₅NO₄	详情	详情
(XI)	59466	ethyl (Z)-3-(4-nitrophenyl)-3-phenyl-2-propenoate		C₁₇H₁₅NO₄	详情	详情
(XIV)	59479	(Z)-3-(4-aminophenyl)-1-{4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl}-3-phenyl-2-propen-1-one		C₂₈H₂₉N₅O	详情	详情
(XV)	59480	4-((Z)-3-{4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl}-3-oxo-1-phenyl-1-propenyl)benzenediazonium chloride		C₂₈H₂₇ClN₆O	详情	详情
(XVI)	15240	2-Hydroxybenzoic acid; Salicylic acid	69-72-7	C₇H₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Horner-Emmons condensation of 4-nitrobenzophenone (IX) with triethyl phosphonoacetate produced a 2:1 mixture of Z and E nitrophenylcinnamic esters (XI) and (X). Alternatively, the desired Z isomer was obtained in a more favorable 8:1 ratio by condensation of (IX) with ethyl (trimethylsilyl)acetate under Peterson reaction conditions. Ester hydrolysis in the mixture (X)+(XI) with K2CO3 in aqueous methanol gave the corresponding mixture of carboxylic acids (XII). Optionally, the pure Z isomer could be isolated by recrystallization from EtOAc. DCC coupling of piperidine (VIII) with either the pure Z-isomer or the Z/E-mixture of carboxylic acids (XII) gave rise to the respective Z/E isomeric amides (XIII). The title Z-(4-aminophenyl)cinnamamide derivative was isolated by column chromatography after catalytic hydrogenation of the nitro group.

参考文献中间体

合成目标

【1】 Ferrando, R.; Carceller, E.; Forn, J.; Ramis, J.; Escamilla, I.; Giral, M.; Merlos, M.; Salas, J.; García-Rafanell, J.; Novel azo derivatives prodrugs of 5-aminosalicylic acid and amino derivatives with potent platelet activating factor antagonist activity. J Med Chem 2001, 44, 18, 3001.
【2】 Carceller, E.; Jimenez, P.J.; Salas, J.; Almansa, C.; Bartroli, J.; Merlos, M.; Giral, M.; Balsa, D.; Ferrando, R.; Garcia-Rafanell, J.; Forn, J. (J. Uriach & Cía., SA); Azo derivs. of 5-aminosalicylic acid for treatment of inflammatory bowel disease. EP 0790998; ES 2104513; ES 2106682; JP 1999501939; US 5747477; WO 9709329 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIIa)	59467	(E)-3-(4-nitrophenyl)-3-phenyl-2-propenoic acid		C₁₅H₁₁NO₄	详情	详情
(XIIb)	59468	(Z)-3-(4-nitrophenyl)-3-phenyl-2-propenoic acid		C₁₅H₁₁NO₄	详情	详情
(XIIIa)	59469	(E)-1-{4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl}-3-(4-nitrophenyl)-3-phenyl-2-propen-1-one		C₂₈H₂₇N₅O₃	详情	详情
(XIIIb)	59470	(Z)-1-{4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl}-3-(4-nitrophenyl)-3-phenyl-2-propen-1-one		C₂₈H₂₇N₅O₃	详情	详情
(VIII)	59463	2-methyl-1-(4-piperidinylmethyl)-1H-imidazo[4,5-c]pyridine		C₁₃H₁₈N₄	详情	详情
(IX)	59464	4-Nitrobenzophenone; p-Nitrobenzophenone	1144-74-7	C₁₃H₉NO₃	详情	详情
(X)	59465	ethyl (E)-3-(4-nitrophenyl)-3-phenyl-2-propenoate		C₁₇H₁₅NO₄	详情	详情
(XI)	59466	ethyl (Z)-3-(4-nitrophenyl)-3-phenyl-2-propenoate		C₁₇H₁₅NO₄	详情	详情

Extended Information