1-(9-chloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl)-N-methyl-1H-imidazole-4-carboxamide -Drug Synthesis Database

【结构式】

【分子编号】58548

【品名】1-(9-chloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl)-N-methyl-1H-imidazole-4-carboxamide

【CA登记号】

【分子式】C₁₅H₁₃ClN₈O

【分子量】356.77424

【元素组成】C 50.5% H 3.67% Cl 9.94% N 31.41% O 4.48%

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)

The condensation between diethyl ethoxymethylenemalonate (I) and 5-amino-1-ethylpyrazole (II) afforded the enamino malonate (III). Cyclization of (III) upon heating at 255 C in diphenyl ether produced the pyrazolopyridine (IV). This was subsequently chlorinated to (V) in refluxing phosphoryl chloride. Alternatively, enamino malonate (III) was directly converted to the chloro pyrazolopyridine (V) by treatment with POCl3. Nitrile (VI) was prepared by displacement of the chloro group of (V) with cyanide in the presence of a phase-transfer catalyst. Cyclization of the cyano ester (VI) with hydrazine led to the pyrazolopyridopyridiazine tricyclic system (VII). Diazotization of amine (VII) generated the dioxo derivative (VIII), which was chlorinated with POCl3 to yield the dichloro derivative (IX). Selective displacement of the 6-chloro group of (IX) with the imidazole carboxamide (X) produced the imidazolyl derivative (XI).

参考文献中间体

合成目标

【1】 Kim, S.; Wang, Y.; Yu, G.; Macor, J.; Chung, H.-J.; Humora, M.; Katipally, K. (Bristol-Myers Squibb Co.); Fused pyridopyridazine inhibitors of cGMP phosphodiesterase. EP 1165521; JP 2002540102; US 6316438; WO 0056719 .

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)	14088	Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate	87-13-8	C₁₀H₁₆O₅	详情	详情
(II)	40098	1-ethyl-1H-pyrazol-5-amine; 1-ethyl-1H-pyrazol-5-ylamine	3528-58-3	C₅H₉N₃	详情	详情
(III)	40099	diethyl 2-[[(1-ethyl-1H-pyrazol-5-yl)amino]methylene]malonate		C₁₃H₁₉N₃O₄	详情	详情
(IV)	40100	ethyl 1-ethyl-4-hydroxy-1H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₁H₁₃N₃O₃	详情	详情
(V)	58542	ethyl 4-chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₁H₁₂ClN₃O₂	详情	详情
(VI)	58543	ethyl 4-cyano-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₂H₁₂N₄O₂	详情	详情
(VII)	58544	9-amino-3-ethyl-3,7-dihydro-6H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-one		C₁₀H₁₀N₆O	详情	详情
(VIII)	58545	3-ethyl-7,8-dihydro-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazine-6,9-dione		C₁₀H₉N₅O₂	详情	详情
(IX)	58546	6,9-dichloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazine		C₁₀H₇Cl₂N₅	详情	详情
(X)	58547	N-methyl-1H-imidazole-4-carboxamide		C₅H₇N₃O	详情	详情
(XI)	58548	1-(9-chloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl)-N-methyl-1H-imidazole-4-carboxamide		C₁₅H₁₃ClN₈O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

The intermediate benzylamine derivative (XIII) was prepared by chlorination of 4-methoxybenzylamine (XII) employing either chlorine in HOAc or sulfuryl chloride. The 9-chloro group of (XI) was finally displaced with amine (XII) by heating at 170 C in a pressure tube to furnish the target 6,9-disubstituted tricyclic compound.

参考文献中间体

合成目标

【1】 Kim, S.; Wang, Y.; Yu, G.; Macor, J.; Chung, H.-J.; Humora, M.; Katipally, K. (Bristol-Myers Squibb Co.); Fused pyridopyridazine inhibitors of cGMP phosphodiesterase. EP 1165521; JP 2002540102; US 6316438; WO 0056719 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	58548	1-(9-chloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl)-N-methyl-1H-imidazole-4-carboxamide		C₁₅H₁₃ClN₈O	详情	详情
(XII)	15098	4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine	2393-23-9	C₈H₁₁NO	详情	详情
(XIII)	51978	(3-chloro-4-methoxyphenyl)methanamine; 3-chloro-4-methoxybenzylamine		C₈H₁₀ClNO	详情	详情

Extended Information