1-(4-Fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)piperazino]-1-butanone -Drug Synthesis Database

【结构式】

【分子编号】11427

【品名】1-(4-Fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)piperazino]-1-butanone

【CA登记号】

【分子式】C₁₈H₂₀F₂N₄O

【分子量】346.3799664

【元素组成】C 62.42% H 5.82% F 10.97% N 16.18% O 4.62%

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)

A new synthesis for [18F]-labeled BMY-14802 has been reported: The compound can be prepared by two related ways: 1) The fluorination of 4-(cyclopropylcarbonyl)nitrobenzene (I) with [18F]-FK and Kryptofix 2.2.2 gives 4-fluorophenyl cyclopropyl methanone (II), which is treated with HCl in methanol yielding 4-chloro-1-(4-fluorophenyl)-1-butanone (III). The condensation of (III) with 5-fluoro-2-piperazinopyrimidine (IV) affords 1-(4-fluorophenyl)-4-[4-(5-fluoropyrimidin-2-yl)piperazin-1-yl]-1-butan one (V), which is finally reduced with NaBH4 in methanol. 2) The reduction of butanone (III) with NaBH4 in methanol gives 4-chloro-1-(4-fluorophenyl)-1-butanol (VI), which is then condensed with pyrimidine (IV) as before.

参考文献中间体

合成目标

【1】 Yevich, J.P.; Frick, M.P.; Shiue, G.G.; Huang, H.; Pleus, R.C.; Shiue, C.-Y.; Bai, L.-Q.; Catt, J.D.; Rysavy, J.A.; Fluorine-18 labeled BMY 14802: Synthesis and anatomical distribution in rodents. J Label Compd Radiopharm 1993, 32, 501.

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)	11423	Cyclopropyl(4-nitrophenyl)methanone		C₁₀H₉NO₃	详情	详情
(II)	11424	Cyclopropyl(4-fluorophenyl)methanone		C₁₀H₉FO	详情	详情
(II)	27427	cyclopropyl(4-fluorophenyl)methanone	772-31-6	C₁₀H₉FO	详情	详情
(III)	11425	4-Chloro-1-(4-fluorophenyl)-1-butanone		C₁₀H₁₀ClFO	详情	详情
(III)	35864	4-chloro-1-(4-fluorophenyl)-1-butanone	3874-54-2	C₁₀H₁₀ClFO	详情	详情
(IV)	11426	5-Fluoro-2-piperazinopyrimidine		C₈H₁₁FN₄	详情	详情
(V)	11427	1-(4-Fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)piperazino]-1-butanone		C₁₈H₂₀F₂N₄O	详情	详情
(V)	28204	1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanone		C₁₈H₂₀F₂N₄O	详情	详情
(VI)	11428	4-Chloro-1-(4-fluorophenyl)-1-butanol		C₁₀H₁₂ClFO	详情	详情
(VI)	45061	4-chloro-1-(4-fluorophenyl)-1-butanol		C₁₀H₁₂ClFO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

A new synthesis of [18F]-labeled BMY-14802 has been described: The fluorination of 4-(cyclopropylcarbonyl)nitrobenzene (I) with [18F]-CsF in DMSO - 5% water at 180 C gives 4-fluorophenylcyclopropylmethanone (II), which is treated with HCl in methanol, yielding 4-chloro-1-(4-fluorophenyl)-1-butanone (III). The condensation of (III) with 5-fluoro-2-piperazinopyrimidine (VI) affords 1-(4-fluorophenyl)-4-[4-(5-fluoropyrimidin-2-yl)piperazin-1-yl]-1-butan one (V), which is finally reduced with NaBH4 in methanol.

参考文献中间体

合成目标

【1】 Shea, C.; Taylor, D.P.; Ding, Y.S.; Wolf, A.P.; Logan, J.; Volkow, N.D.; Gatley, S.J.; Fowler, J.S.; Dewey, S.L.; Synthesis and PET studies of fluorine-18-BMY-14802 - A potential antipsychotic drug. J Nucl Med 1993, 34, 2, 246.

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)	11423	Cyclopropyl(4-nitrophenyl)methanone		C₁₀H₉NO₃	详情	详情
(II)	11424	Cyclopropyl(4-fluorophenyl)methanone		C₁₀H₉FO	详情	详情
(II)	27427	cyclopropyl(4-fluorophenyl)methanone	772-31-6	C₁₀H₉FO	详情	详情
(III)	11431	4-Chloro-1-(4-fluorophenyl)-1-butanone		C₁₀H₁₀ClFO	详情	详情
(III)	35864	4-chloro-1-(4-fluorophenyl)-1-butanone	3874-54-2	C₁₀H₁₀ClFO	详情	详情
(IV)	11426	5-Fluoro-2-piperazinopyrimidine		C₈H₁₁FN₄	详情	详情
(V)	11427	1-(4-Fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)piperazino]-1-butanone		C₁₈H₂₀F₂N₄O	详情	详情
(V)	28024	(2S)-2-(chloromethyl)-1-ethylpyrrolidine		C₇H₁₄ClN	详情	详情

Extended Information