DPC-602, -Drug Synthesis Database

【结构式】

【药物名称】DPC-602

【化学名称】1-[2-(Aminomethyl)phenyl]-N-(2'-sulfamoyl-3-fluorobiphenyl-4-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide hydrochloride

【CA登记号】228258-45-5, 228258-87-5 (monotrifluoroacetate)

【分子式】C₂₄H₂₀ClF₄N₅O₃S

【分子量】569.9693

【开发单位】Bristol-Myers Squibb (Originator)

【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Coagulation Factor Xa Inhibitors

合成路线1 合成路线2

合成路线1

The condensation between 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (I) and 2-hydrazinobenzoic acid (II) in refluxing HOAc afforded the pyrazole derivative (III). After conversion of (III) into the corresponding acid chloride (IV) by using SOCl2, treatment with ammonium hydroxide provided amide (V). Dehydration of amide (V) employing trichloroacetyl chloride and Et3N yielded nitrile (VI), which was reduced to the primary amine (VII) with NaBH4 and CoCl2. After protection of the amino group of (VII) as the N-Boc derivative (VIII), oxidative cleavage of the furan ring with KMnO4 produced the carboxylic acid (IX), which was further activated as the acid chloride (X) upon treatment with oxalyl chloride.

参考文献中间体

【1】 Bostrom, L.L.; Pinto, D.J.P.; Galemmo, R.A. Jr.; Rossi, K.A. (DuPont Pharmaceuticals Co.); Nitrogen containing heteroaromatics with ortho-substd. P1's as factor Xa inhibitors. EP 1042299; WO 9932454 .

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)	47956	4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione; 1-(2-Furanyl)-4,4,4-trifluoro-1,3-butanedione	326-90-9	C₈H₅F₃O₃	详情	详情
(II)	47957	2-hydrazinobenzoic acid	52356-01-1	C₇H₈N₂O₂	详情	详情
(III)	47958	2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoic acid		C₁₅H₉F₃N₂O₃	详情	详情
(IV)	47958	2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoic acid		C₁₅H₉F₃N₂O₃	详情	详情
(V)	47959	2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoyl chloride		C₁₅H₈ClF₃N₂O₂	详情	详情
(VI)	47960	2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzamide		C₁₅H₁₀F₃N₃O₂	详情	详情
(VII)	47961	2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile		C₁₅H₈F₃N₃O	详情	详情
(VIII)	47962	2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylamine; [2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]methanamine		C₁₅H₁₂F₃N₃O	详情	详情
(IX)	47963	tert-butyl 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylcarbamate		C₂₀H₂₀F₃N₃O₃	详情	详情
(X)	47964	1-(2-[[(tert-butoxycarbonyl)amino]methyl]phenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid		C₁₇H₁₈F₃N₃O₄	详情	详情
(XI)	47965	tert-butyl 2-[5-(chlorocarbonyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylcarbamate		C₁₇H₁₇ClF₃N₃O₃	详情	详情

合成路线2

Coupling of acid chloride (X) with the biphenyl amine (XI) gave the corresponding amide (XII). The tert-butyl and Boc protecting groups of (XII) were finally cleaved by treatment with trifluoroacetic acid.

参考文献中间体

【1】 Bostrom, L.L.; Pinto, D.J.P.; Galemmo, R.A. Jr.; Rossi, K.A. (DuPont Pharmaceuticals Co.); Nitrogen containing heteroaromatics with ortho-substd. P1's as factor Xa inhibitors. EP 1042299; WO 9932454 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	47965	tert-butyl 2-[5-(chlorocarbonyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylcarbamate	C₁₇H₁₇ClF₃N₃O₃	详情	详情
(XI)	47966	4'-amino-N-(tert-butyl)-3'-fluoro[1,1'-biphenyl]-2-sulfonamide	C₁₆H₁₉FN₂O₂S	详情	详情
(XII)	47967	tert-butyl 2-[5-[([2'-[(tert-butylamino)sulfonyl]-3-fluoro[1,1'-biphenyl]-4-yl]amino)carbonyl]-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylcarbamate	C₃₃H₃₅F₄N₅O₅S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)