5-amino-3-(4-methoxyphenyl)indeno[1,2-c]pyrazol-4(2H)-one -Drug Synthesis Database

【结构式】

【分子编号】34486

【品名】5-amino-3-(4-methoxyphenyl)indeno[1,2-c]pyrazol-4(2H)-one

【CA登记号】

【分子式】C₁₇H₁₃N₃O₂

【分子量】291.30924

【元素组成】C 70.09% H 4.5% N 14.42% O 10.98%

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：(VII)

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'-methoxyacetophenone (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

合成目标

【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)	11041	4-Methoxyacetophenone; 1-(4-Methoxyphenyl)-1-ethanone	100-06-1	C₉H₁₀O₂	详情	详情
(V)	34484	N-[2-(4-methoxybenzoyl)-1,3-dioxo-2,3-dihydro-1H-inden-4-yl]acetamide		C₁₉H₁₅NO₅	详情	详情
(VI)	34485	4-amino-2-(4-methoxybenzoyl)-1H-indene-1,3(2H)-dione		C₁₇H₁₃NO₄	详情	详情
(VII)	34486	5-amino-3-(4-methoxyphenyl)indeno[1,2-c]pyrazol-4(2H)-one		C₁₇H₁₃N₃O₂	详情	详情
(VIII)	34487	phenyl 3-(4-methoxyphenyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-ylcarbamate		C₂₄H₁₇N₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Catalytic hydrogenation of dimethyl 3-nitrophthalate (I) in the presence of Pd/C afforded the corresponding amino derivative (II), which was subsequently acetylated with Ac2O in pyridine yielding amide (III). Claisen condensation of diester (III) with 4'-methoxyacetophenone (IV) using NaH in hot DMF furnished the indandione (V). The tricarbonyl intermediate (V) was then treated with hydrazine to give the indenopyrazole (VI) as a single regioisomer. Acidic hydrolysis of the acetamide function of (VI) provided amine (VII). This was finally converted to the target formamide derivative upon heating with neat formic acid.

参考文献中间体

合成目标

【1】 Nugiel, D.A.; et al.; Indenopyrazoles as novel cyclin dependen kinase (CDK) inhibitors. J Med Chem 2001, 44, 9, 1334.
【2】 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
(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)	11041	4-Methoxyacetophenone; 1-(4-Methoxyphenyl)-1-ethanone	100-06-1	C₉H₁₀O₂	详情	详情
(V)	34484	N-[2-(4-methoxybenzoyl)-1,3-dioxo-2,3-dihydro-1H-inden-4-yl]acetamide		C₁₉H₁₅NO₅	详情	详情
(VI)	49762	N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl]acetamide		C₁₉H₁₅N₃O₃	详情	详情
(VII)	34486	5-amino-3-(4-methoxyphenyl)indeno[1,2-c]pyrazol-4(2H)-one		C₁₇H₁₃N₃O₂	详情	详情

Extended Information