(4-nitrophenyl)(1-piperazinyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】20011

【品名】(4-nitrophenyl)(1-piperazinyl)methanone

【CA登记号】

【分子式】C₁₁H₁₃N₃O₃

【分子量】235.24264

【元素组成】C 56.16% H 5.57% N 17.86% O 20.4%

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：(IX)

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2

该中间体在本合成路线中的序号：(III)

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

合成路线3

该中间体在本合成路线中的序号：(III)

The acylation of piperazine (II) with 4-nitrobenzoyl chloride (I) afforded a mixture of monoacylated (III) and diacylated (IV) products, which were separated by chromatography. Subsequent alkylation of monosubstituted piperazine (III) with 4-nitrophenethyl bromide (V) in the presence of K2CO3 and NaI yielded the title compound.

参考文献中间体

合成目标

【1】 Kanojia, R.M.; Kauffman, J.; Salata, J.J.; Synthesis and class III type antiarrhythmic activity of 4-aroyl (and aryl)-1-aralkylpiperazines. Bioorg Med Chem Lett 2000, 10, 24, 2819.
【2】 Kanojia, R.M.; et al.; Synthesis and selective class III type antiarrhythmic activity of 4-aroyl (and aryl)-1-aralkylpiperazines. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 204.

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)	40947	[4-(4-nitrobenzoyl)-1-piperazinyl](4-nitrophenyl)methanone		C₁₈H₁₆N₄O₆	详情	详情
(V)	19191	1-(2-bromoethyl)-4-nitrobenzene	5339-26-4	C₈H₈BrNO₂	详情	详情

Extended Information