7-isoquinolinamine; 7-isoquinolinylamine -Drug Synthesis Database

【结构式】

【分子编号】39253

【品名】7-isoquinolinamine; 7-isoquinolinylamine

【CA登记号】23707-37-1

【分子式】C₉H₈N₂

【分子量】144.176

【元素组成】C 74.98% H 5.59% N 19.43%

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：(I)

7-Aminoisoquinoline (I) was diazotized and then reduced with SnCl2 to afford the tin double salt of hydrazino isoquinoline (II), which was subsequently condensed with ethyl 2,4-dioxopentanoate oxime (III) yielding isoquinolinyl pyrazole (IV) as the major regioisomer. Displacement of the methyl ester group with biphenyl amine (V) in the presence of Me3Al furnished amide (VI). Introduction of the 1-amino moiety was accomplished via formation of the N-oxide (VII), followed by rearrangement with tosyl chloride and further displacement with ethanolamine. Finally, deprotection of the N-tert-butyl group with trifluoroacetic acid gave rise to the title compound.

参考文献中间体

合成目标

【1】 Quan, M.L.; Clark, C.G.; Lam, P.Y.; Pinto, D.J.-P.; Han, Q.; Fevig, J.M.; Li, R.; Pruitt, J.R.; Dominguez, C. (DuPont Pharmaceuticals Co.); Novel guanidine mimics as factor Xa inhibitors. EP 0991638; WO 9857951 .

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)	39253	7-isoquinolinamine; 7-isoquinolinylamine	23707-37-1	C₉H₈N₂	详情	详情
(II)	39254	7-hydrazinoisoquinoline		C₉H₉N₃	详情	详情
(III)	39255	ethyl 2-(hydroxyimino)-4-oxopentanoate		C₇H₁₁NO₄	详情	详情
(IV)	39256	methyl 1-(7-isoquinolinyl)-3-methyl-1H-pyrazole-5-carboxylate		C₁₅H₁₃N₃O₂	详情	详情
(V)	23363	4'-amino-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide		C₁₆H₂₀N₂O₂S	详情	详情
(VI)	39257	N-[2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]-1-(7-isoquinolinyl)-3-methyl-1H-pyrazole-5-carboxamide		C₃₀H₂₉N₅O₃S	详情	详情
(VII)	39258	7-[5-[([2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]amino)carbonyl]-3-methyl-1H-pyrazol-1-yl]-2-isoquinoliniumolate		C₃₀H₂₉N₅O₄S	详情	详情
(VIII)	39259	1-(1-amino-7-isoquinolinyl)-N-[2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]-3-methyl-1H-pyrazole-5-carboxamide		C₃₀H₃₀N₆O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

7-Aminoisoquinoline (I) was diazotized with NaNO2/HCl and then reduced with SnCl2 to afford the tin double salt of hydrazino isoquinoline (II), which was subsequently condensed with ethyl 2,4-dioxopentanoate oxime (III) yielding isoquinolinyl pyrazole (IV) as the major regioisomer. Displacement of the methyl ester group of (IV) with biphenyl amine (V) in the presence of Me3Al furnished amide (VI). Introduction in (VI) of the 1-amino moiety was accomplished via formation of the N-oxide (VII) with MCPBA, followed by rearrangement with tosyl chloride and finally displacement with ethanolamine.

参考文献中间体

合成目标

【1】 Quan, M.L.; Clark, C.G.; Lam, P.Y.; Pinto, D.J.-P.; Han, Q.; Fevig, J.M.; Li, R.; Pruitt, J.R.; Dominguez, C. (DuPont Pharmaceuticals Co.); Novel guanidine mimics as factor Xa inhibitors. EP 0991638; WO 9857951 .

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)	39253	7-isoquinolinamine; 7-isoquinolinylamine	23707-37-1	C₉H₈N₂	详情	详情
(II)	39254	7-hydrazinoisoquinoline		C₉H₉N₃	详情	详情
(III)	39255	ethyl 2-(hydroxyimino)-4-oxopentanoate		C₇H₁₁NO₄	详情	详情
(IV)	39256	methyl 1-(7-isoquinolinyl)-3-methyl-1H-pyrazole-5-carboxylate		C₁₅H₁₃N₃O₂	详情	详情
(V)	39260	2'-(methylsulfonyl)[1,1'-biphenyl]-4-amine; 2'-(methylsulfonyl)[1,1'-biphenyl]-4-ylamine		C₁₃H₁₃NO₂S	详情	详情
(VI)	39261	1-(7-isoquinolinyl)-3-methyl-N-[2'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]-1H-pyrazole-5-carboxamide		C₂₇H₂₂N₄O₃S	详情	详情
(VII)	39262	7-[3-methyl-5-([[2'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]amino]carbonyl)-1H-pyrazol-1-yl]-2-isoquinoliniumolate		C₂₇H₂₂N₄O₄S	详情	详情

Extended Information