2-chloro-3-quinolinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】61948

【品名】2-chloro-3-quinolinecarboxylic acid

【CA登记号】

【分子式】C₁₀H₆ClNO₂

【分子量】207.61588

【元素组成】C 57.85% H 2.91% Cl 17.08% N 6.75% O 15.41%

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：(V)

Alkylation of 4-amino-3-nitrophenol (I) with 1-(2-chloroethyl)piperidine (II) provides ether (III). Subsequent nitro group reduction in (III) to afford diamine (IV) is performed by means of zinc powder in AcOH. Coupling of diamine (IV) with 2-chloroquinoline-3-carboxylic acid (V) furnishes amide (VI). Then, intramolecular cyclization of amino amide (VI) with Burgess reagent, followed by hydrolysis in boiling 6 M HCl gives rise to the title benzimidazolyl quinolinone.

参考文献中间体

合成目标

【1】 Hungate, R.W.; Fraley, M.E.; Hambaugh, S.R. (Merck & Co., Inc.); Tyrosine kinase inhibitors. JP 2003512353; US 6479512; WO 0128993 .

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)	61945	4-amino-3-nitrophenol		C₆H₆N₂O₃	详情	详情
(II)	10117	1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine	1932-03-2	C₇H₁₄ClN	详情	详情
(III)	61946	2-nitro-4-[2-(1-piperidinyl)ethoxy]aniline; 2-nitro-4-[2-(1-piperidinyl)ethoxy]phenylamine		C₁₃H₁₉N₃O₃	详情	详情
(IV)	61947	2-amino-4-[2-(1-piperidinyl)ethoxy]phenylamine; 4-[2-(1-piperidinyl)ethoxy]-1,2-benzenediamine		C₁₃H₂₁N₃O	详情	详情
(V)	61948	2-chloro-3-quinolinecarboxylic acid		C₁₀H₆ClNO₂	详情	详情
(VI)	61949	N-{2-amino-4-[2-(1-piperidinyl)ethoxy]phenyl}-2-chloro-3-quinolinecarboxamide		C₂₃H₂₅ClN₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Treatment of 2-chloroquinoline-3-carboxylic acid (I) with oxalyl chloride affords acid chloride (II), which is subsequently coupled with methyl 3,4-diaminobenzoate (III) to yield amide (IV). Intramolecular cyclization of amino amide (IV) with Burgess reagent in refluxing THF produces the benzimidazole (V). Then, acidic hydrolysis of both methyl ester and chloroquinoline functions of (V) gives rise to the carboxylic acid (VI). Coupling of (VI) with N-Boc-piperazine (VII) furnishes amide (VIII). The N-Boc protecting group of (VIII) is finally removed by treatment with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Hungate, R.W.; Fraley, M.E.; Hambaugh, S.R. (Merck & Co., Inc.); Tyrosine kinase inhibitors. JP 2003512353; US 6479512; WO 0128993 .

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)	61948	2-chloro-3-quinolinecarboxylic acid		C₁₀H₆ClNO₂	详情	详情
(II)	61950	2-chloro-3-quinolinecarbonyl chloride		C₁₀H₅Cl₂NO	详情	详情
(III)	34921	3-cyanobenzoyl chloride	1711-11-1	C₈H₄ClNO	详情	详情
(IV)	61951	methyl 3-amino-4-{[(2-chloro-3-quinolinyl)carbonyl]amino}benzoate		C₁₈H₁₄ClN₃O₃	详情	详情
(V)	61952	methyl 2-(2-chloro-3-quinolinyl)-1H-benzimidazole-5-carboxylate		C₁₈H₁₂ClN₃O₂	详情	详情
(VI)	61953	2-(2-oxo-1,2-dihydro-3-quinolinyl)-1H-benzimidazole-5-carboxylic acid		C₁₇H₁₁N₃O₃	详情	详情
(VII)	13225	N-tert-Butoxycarbonyl piperazine; tert-butyl 1-piperazinecarboxylate;tert-butyl piperazine-1-carboxylate	143238-38-4	C₉H₁₈N₂O₂	详情	详情
(VIII)	61954	tert-butyl 4-{[2-(2-oxo-1,2-dihydro-3-quinolinyl)-1H-benzimidazol-5-yl]carbonyl}-1-piperazinecarboxylate		C₂₆H₂₇N₅O₄	详情	详情

Extended Information