1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】37816

【品名】1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxylic acid

【CA登记号】

【分子式】C₁₂H₉N₃O₂

【分子量】227.22248

【元素组成】C 63.43% H 3.99% N 18.49% O 14.08%

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：(V)

The cyclization of 3-bromophenylhydrazine (I) with 2-(trichloroacetyl)-3-methoxycrotonic acid (II) in refluxing ethanol gives, after chromatographic separation, 1-(3-bromophenyl)-3-methylpyrazole-5-carboxylic acid ethyl ester (III), which by reaction with CuCN in refluxing N-methylpyrrolidone is converted into the 3-cyanophenyl analogue (IV). The hydrolysis of (IV) with LiOH in THF/water affords the corresponding carboxylic acid (V), which by reaction with oxalyl chloride in dichloromethane gives the acyl chloride (VI). The condensation of (VI) with 4'-amino-N-tert-butylbiphenyl-2-sulfonamide (VII) by means of TEA in dichloromethane provides the corresponding amide (VIII), which is finally treated first with HCl in methanol, and then with ammonium carbonate in the same solvent.

参考文献中间体

合成目标

【1】 Orwat, M.J.; Cacciola, J.; Han, Q.; Fevig, J.M.; Pinto, D.J.P.; Rossi, K.A.; Pruitt, J.R.; Quan, M.L. (DuPont Pharmaceuticals Co.); Nitrogen containing heteroaromatics as factor Xa inhibitors. EP 0946508; WO 9828269 .

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)	37812	1-(3-bromophenyl)hydrazine	27246-81-7	C₆H₇BrN₂	详情	详情
(II)	37813	(Z)-4-methoxy-2-(2,2,2-trichloroacetyl)-3-pentenoic acid		C₈H₉Cl₃O₄	详情	详情
(III)	37814	ethyl 1-(3-bromophenyl)-3-methyl-1H-pyrazole-5-carboxylate		C₁₃H₁₃BrN₂O₂	详情	详情
(IV)	37815	ethyl 1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxylate		C₁₄H₁₃N₃O₂	详情	详情
(V)	37816	1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxylic acid		C₁₂H₉N₃O₂	详情	详情
(VI)	37817	1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carbonyl chloride		C₁₂H₈ClN₃O	详情	详情
(VII)	23363	4'-amino-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide		C₁₆H₂₀N₂O₂S	详情	详情
(VIII)	37818	N-[2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]-1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxamide		C₂₈H₂₇N₅O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The cyclization of 3-bromophenylhydrazine (I) with 2-(trichloroacetyl)-3-methoxycrotonic acid (II) in refluxing ethanol gives, after chromatographic separation, 1-(3-bromophenyl)-3-methylpyrazole-5-carboxylic acid ethyl ester (III), which by reaction with CuCN in refluxing N-methylpyrrolidone is converted into the 3-cyanophenyl analogue (IV). The hydrolysis of (IV) with LiOH in THF/water affords the corresponding carboxylic acid (V), which by reaction with oxalyl chloride in dichloromethane gives the acyl chloride (VI). The condensation of (VI) with 2-(2-aminopyrimidin-4-yl)-N-tert-butylbenzenesulfonamide (VII) by means of TEA in dichloromethane provides the corresponding amide (VIII), which is finally treated first with HCl in methanol, and then with ammonium carbonate in the same solvent.

参考文献中间体

合成目标

【1】 Orwat, M.J.; Cacciola, J.; Han, Q.; Fevig, J.M.; Pinto, D.J.P.; Rossi, K.A.; Pruitt, J.R.; Quan, M.L. (DuPont Pharmaceuticals Co.); Nitrogen containing heteroaromatics as factor Xa inhibitors. EP 0946508; WO 9828269 .

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)	37812	1-(3-bromophenyl)hydrazine	27246-81-7	C₆H₇BrN₂	详情	详情
(II)	37813	(Z)-4-methoxy-2-(2,2,2-trichloroacetyl)-3-pentenoic acid		C₈H₉Cl₃O₄	详情	详情
(III)	37814	ethyl 1-(3-bromophenyl)-3-methyl-1H-pyrazole-5-carboxylate		C₁₃H₁₃BrN₂O₂	详情	详情
(IV)	37815	ethyl 1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxylate		C₁₄H₁₃N₃O₂	详情	详情
(V)	37816	1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxylic acid		C₁₂H₉N₃O₂	详情	详情
(VI)	37817	1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carbonyl chloride		C₁₂H₈ClN₃O	详情	详情
(VII)	34823	2-(2-amino-5-pyrimidinyl)-N-(tert-butyl)benzenesulfonamide		C₁₄H₁₈N₄O₂S	详情	详情
(VIII)	37819	N-(5-[2-[(tert-butylamino)sulfonyl]phenyl]-2-pyrimidinyl)-1-(3-cyanophenyl)-3-methyl-1H-pyrazole-5-carboxamide		C₂₆H₂₅N₇O₃S	详情	详情

Extended Information