-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N-[3-(5-Chloro-3-thienyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl]urea

【CA登记号】

【分子式】C₁₅H₉ClN₄O₂S

【分子量】344.78158

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

【药理作用】Oncolytic Drugs, Cyclin-Dependent Kinase Inhibitors, Inhibitors of Signal Transduction Pathways

合成路线1

Dimethyl 3-nitrophthalate (I) was hydrogenated in the presence of Pd/C to give aminophthalate (II), which was acylated with Ac2O in pyridine, yielding acetamidophthalate (III). Condensation of phthalate ester (III) with 4-acetyl-2-chlorothiophene (IV) using NaH in DMF produced triketone (V). After acid hydrolysis of the amide function of (V), the resulting aminoindenetrione (VI) was cyclized with hydrazine hydrate to generate the indenopyrazolone system (VII). Condensation of (VII) with phenyl chloroformate afforded the phenyl carbamate (VIII). This was finally treated with concentrated ammonia to furnish the target urea derivative.

参考文献中间体

【1】 Yue, E.W.; Carini, D.J.; Nugiel, D.A.; Dimeo, S.V. (DuPont Pharmaceuticals Co.); 5-Aminoindeno(1,2-c)pyrazol-4-ones as anti-cancer and anti-proliferative agents. WO 9954308 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(I)	34481	dimethyl 3-nitrophthalate	13365-26-9	C₁₀H₉NO₆	详情	详情
(II)	34482	dimethyl 3-aminophthalate		C₁₀H₁₁NO₄	详情	详情
(III)	34483	dimethyl 3-(acetamido)phthalate		C₁₂H₁₃NO₅	详情	详情
(IV)	34488	1-(5-chloro-3-thienyl)-1-ethanone		C₆H₅ClOS	详情	详情
(V)	34489	N-[2-[(5-chloro-3-thienyl)carbonyl]-1,3-dioxo-2,3-dihydro-1H-inden-4-yl]acetamide		C₁₆H₁₀ClNO₄S	详情	详情
(VI)	34490	4-amino-2-[(5-chloro-3-thienyl)carbonyl]-1H-indene-1,3(2H)-dione		C₁₄H₈ClNO₃S	详情	详情
(VII)	34491	5-amino-3-(5-chloro-3-thienyl)indeno[1,2-c]pyrazol-4(2H)-one		C₁₄H₈ClN₃OS	详情	详情
(VIII)	34492	phenyl 3-(5-chloro-3-thienyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-ylcarbamate		C₂₁H₁₂ClN₃O₃S	详情	详情

Extended Information