ethyl 4-hydroxy-6-iodo-3-quinolinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】44988

【品名】ethyl 4-hydroxy-6-iodo-3-quinolinecarboxylate

【CA登记号】

【分子式】C₁₂H₁₀INO₃

【分子量】343.12081

【元素组成】C 42.01% H 2.94% I 36.99% N 4.08% O 13.99%

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：(III)

The condensation between 4-iodoaniline (I) and diethyl ethoxymethylenemalonate (II) at 130 C, followed by cyclization in diphenyl ether at 250 C, furnished ethyl 4-hydroxy-6-iodoquinoline-3-carboxylate (III). Subsequent reaction of ester (III) with 4-chlorobenzylamine (IV) at 180 C produced the corresponding amide (V). Finally, coupling of (V) with propargyl alcohol (VI) in the presence of CuI and palladium catalyst afforded the desired (hydroxypropynyl)quinoline.

参考文献中间体

合成目标

【1】 Schnute, M.E.; Turner, S.R.; Cudahy, M.M.; Vaillancourt, V.A.; Thaisrivongs, S.; Strohbach, J.W.; Romines, K.R.; Tucker, J.A. (Pharmacia Corp.); 4-Hydroxyquinoline-3-carboxamides and hydrazides as antiviral agents. EP 1042295; US 6093732; WO 9932450 .

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)	26393	4-iodoaniline; 4-iodophenylamine	540-37-4	C₆H₆IN	详情	详情
(II)	14088	Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate	87-13-8	C₁₀H₁₆O₅	详情	详情
(III)	44988	ethyl 4-hydroxy-6-iodo-3-quinolinecarboxylate		C₁₂H₁₀INO₃	详情	详情
(IV)	23378	(4-chlorophenyl)methanamine; 4-chlorobenzylamine	104-86-9	C₇H₈ClN	详情	详情
(V)	44989	N-(4-chlorobenzyl)-4-hydroxy-6-iodo-3-quinolinecarboxamide		C₁₇H₁₂ClIN₂O₂	详情	详情
(VI)	16664	Propargyl Alcohol; 2-propyn-1-ol	107-19-7	C₃H₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The 4-hydroxyquinoline (III) was synthesized via Gould-Jacobs reaction from 4-iodoaniline (I) and diethyl ethoxymethylenemalonate (II). Displacement of the ethyl ester group with 4-chlorobenzylamine (IV) at 180 C furnished the chlorobenzyl amide (V). Subsequent palladium-catalyzed carbonylation of iodide (V) provided the methyl carboxylate (VI), which was further reduced to alcohol (VII) using LiAlH4. Methylation of the hydroxyquinoline (VII) with iodomethane gave rise to the N-methyl quinolone (VIII). After conversion of the alcohol function of (VIII) to the corresponding mesylate (IX), displacement with morpholine (X) yielded the target morpholinomethyl quinolone.

参考文献中间体

合成目标

【1】 Turner, S.R.; Strohbach, J.W.; Scott, A.; Schnute, M.E.; Vaillancourt, V.A.; Thaisrivongs, S. (Pharmacia Corp.); 4-Oxo-1,4-dihydro-3-quinolinecarboxamides as antiviral agents. EP 1140851; WO 0040563 .

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)	26393	4-iodoaniline; 4-iodophenylamine	540-37-4	C₆H₆IN	详情	详情
(II)	14088	Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate	87-13-8	C₁₀H₁₆O₅	详情	详情
(III)	44988	ethyl 4-hydroxy-6-iodo-3-quinolinecarboxylate		C₁₂H₁₀INO₃	详情	详情
(IV)	23378	(4-chlorophenyl)methanamine; 4-chlorobenzylamine	104-86-9	C₇H₈ClN	详情	详情
(V)	44989	N-(4-chlorobenzyl)-4-hydroxy-6-iodo-3-quinolinecarboxamide		C₁₇H₁₂ClIN₂O₂	详情	详情
(VI)	49889	methyl 3-[[(4-chlorobenzyl)amino]carbonyl]-4-hydroxy-6-quinolinecarboxylate		C₁₉H₁₅ClN₂O₄	详情	详情
(VII)	49890	N-(4-chlorobenzyl)-4-hydroxy-6-(hydroxymethyl)-3-quinolinecarboxamide		C₁₈H₁₅ClN₂O₃	详情	详情
(VIII)	49891	N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide		C₁₉H₁₇ClN₂O₃	详情	详情
(IX)	49892	(3-[[(4-chlorobenzyl)amino]carbonyl]-1-methyl-4-oxo-1,4-dihydro-6-quinolinyl)methyl methanesulfonate		C₂₀H₁₉ClN₂O₅S	详情	详情
(X)	10338	1-[(4S,5S)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-(trityloxy)-1-ethanone		C₃₃H₄₂O₅Si	详情	详情

Extended Information