4-chloro-7-(trifluoromethyl)quinoline -Drug Synthesis Database

【结构式】

【分子编号】20003

【品名】4-chloro-7-(trifluoromethyl)quinoline

【CA登记号】346-55-4

【分子式】C₁₀H₅ClF₃N

【分子量】231.6043496

【元素组成】C 51.86% H 2.18% Cl 15.31% F 24.61% N 6.05%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

The earlier synthesis starts with the reaction of 4-chloro-7-(trifluoromethyl)quinoline (I) with 4-aminobenzoic acid (II) in ethanol-HCl giving 4-(4-carboxyphenylamino)-7-(trifluoromethyl)quinoline (III), which is converted to its acyl chloride (IV) by treatment with SOCl2. The reaction of (IV) with piperazine (V) yields 1-[4-[7-(trifluoromethyl)quinolin-4-ylamino]benzoyl]piperazine (VI), which is finally acylated with 4-fluorobenzenesulfonyl chloride (VII) to give U-54669 F. However, this method is not economically efficient, since the most expensive compound [quinoline (I)] is already used in the first step of the synthesis.

参考文献中间体

合成目标

【1】 McCall, J.M. (Pharmacia Corp.); Aminoquinolines. GB 2021567 .

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)	20003	4-chloro-7-(trifluoromethyl)quinoline	346-55-4	C₁₀H₅ClF₃N	详情	详情
(II)	20004	p-aminobenzoic acid; 4-aminobenzoic acid	150-13-0	C₇H₇NO₂	详情	详情
(III)	20005	4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoic acid		C₁₇H₁₁F₃N₂O₂	详情	详情
(IV)	20006	4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl chloride		C₁₇H₁₀ClF₃N₂O	详情	详情
(V)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(VI)	20008	1-piperazinyl(4-[[7-(trifluoromethyl)-4-quinolinyl]amino]phenyl)methanone		C₂₁H₁₉F₃N₄O	详情	详情
(VII)	12292	4-Fluorobenzenesulfonyl chloride	349-88-2	C₆H₄ClFO₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

3) The third synthesis starts with acylation of piperazine (V) with 4-nitrobenzoyl chloride (VIII) to the corresponding amide (IX), which is sulfonated with 4-fluorobenzenesulfonyl chloride (VII) yielding 1-(4-nitrobenzoyl)-4-(4-fluorobenzenesulfonyl)piperazine (X). The reduction of the nitro group of (X) affords the corresponding amino derivative (XI) [also obtained by previous reduction of (IX) to 1-(4-aminobenzoyl)piperazine (XII) and sulfonation with (VII) as before]. Finally, (XI) is condensed with quinoline (I) to give U-54669 F. This is an economically better method since the most expensive product [quinoline (I)] is used in the last step of the synthesis, so obtaining better yields.

参考文献中间体

合成目标

【1】 McCall, J.M. (Pharmacia Corp.); Process for 4-amino quinolines. EP 0215902; JP 1987502339; WO 8605489 .

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)	20003	4-chloro-7-(trifluoromethyl)quinoline	346-55-4	C₁₀H₅ClF₃N	详情	详情
(VIII)	20010	1-(4-nitrophenyl)-1-ethanone	100-19-6	C₈H₇NO₃	详情	详情
(IX)	20011	(4-nitrophenyl)(1-piperazinyl)methanone		C₁₁H₁₃N₃O₃	详情	详情
(X)	20012	[4-[(4-fluorophenyl)sulfonyl]-1-piperazinyl](4-nitrophenyl)methanone		C₁₇H₁₆FN₃O₅S	详情	详情
(XI)	20013	(4-aminophenyl)[4-[(4-fluorophenyl)sulfonyl]-1-piperazinyl]methanone		C₁₇H₁₈FN₃O₃S	详情	详情
(XII)	20014	(4-aminophenyl)(1-piperazinyl)methanone		C₁₁H₁₅N₃O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

The condensation of 4-nitrobenzoyl chloride (I) with piperazine (II) in water by means of KOH gives 4-nitrobenzoylpiperazine (III), which is reduced with H2 over Pd/C in methanol yielding 4-aminobenzoyl piperazine (IV). The condensation of (IV) with 4-chloro-7-trifluoromethylquinoline (V) by means of HCl in refluxing ethanol affords 4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine (VI), which is finally acylated with 4-fluorobenzenesulfonyl chloride (VII) by means of triethylamine in THF.

参考文献中间体

合成目标

【1】 McCall, J.M. (Pharmacia Corp.); Aminoquinolines. GB 2021567 .
【2】 Castaner, J.; Serradell, M.N.; U-54669-F. Drugs Fut 1984, 9, 1, 36.

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)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(II)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(III)	20011	(4-nitrophenyl)(1-piperazinyl)methanone		C₁₁H₁₃N₃O₃	详情	详情
(IV)	20014	(4-aminophenyl)(1-piperazinyl)methanone		C₁₁H₁₅N₃O	详情	详情
(V)	20003	4-chloro-7-(trifluoromethyl)quinoline	346-55-4	C₁₀H₅ClF₃N	详情	详情
(VI)	20008	1-piperazinyl(4-[[7-(trifluoromethyl)-4-quinolinyl]amino]phenyl)methanone		C₂₁H₁₉F₃N₄O	详情	详情
(VII)	12292	4-Fluorobenzenesulfonyl chloride	349-88-2	C₆H₄ClFO₂S	详情	详情

Extended Information