1-piperazinyl(4-[[7-(trifluoromethyl)-4-quinolinyl]amino]phenyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】20008

【品名】1-piperazinyl(4-[[7-(trifluoromethyl)-4-quinolinyl]amino]phenyl)methanone

【CA登记号】

【分子式】C₂₁H₁₉F₃N₄O

【分子量】400.4034296

【元素组成】C 62.99% H 4.78% F 14.23% N 13.99% O 4%

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：(VI)

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：(VI)

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