cyclopropyl(4-fluorophenyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】27427

【品名】cyclopropyl(4-fluorophenyl)methanone

【CA登记号】772-31-6

【分子式】C₁₀H₉FO

【分子量】164.1792632

【元素组成】C 73.16% H 5.53% F 11.57% O 9.75%

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：(II)

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：(II)

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

合成路线3

该中间体在本合成路线中的序号：(VIIII)

This compound can be obtained by two similar ways: 1) The hydrogenation of the double bond of 3-(4-imidazolyl)propenoic acid (I) with H2 over Pd/C in water gives the propionic acid (II), which is esterified with ethanol and sulfuric acid to the ethyl ester (III). The protection of (III) with triphenylmethyl chloride by means of triethylamine in DMF affords the trityl derivative (IV), which is reduced with LiAlH4 in THF yielding 3-(4-imidazolyl)propanol (V). The condensation of (V) with the phenol (VI) by means of triphenylphosphine and diethyl azodicarboxylate in THF provides the ether (VII), which deprotected with HCl in hot THF. 2) Alternatively, propanol (V) can be condensed with cyclopropyl 4-fluorophenyl ketone (VIII) by means of NaH in refluxing toluene to give the previously reported ether (VII).

参考文献中间体

合成目标

【1】 Krause, M.; Stark, H.; Sadek, B.; et al.; Novel histamine H3-receptor antagonists with carbonyl-substituted 4-(3-(phenoxy) propyl)-1H-imidazole structures like ciproxifan and related compounds. J Med Chem 2000, 43, 21, 3987.
【2】 Ligneau, X.; Stark, H.; Elz, S.; Teriuk, W.; Schwartz, J.-C.; Athmani, S.; Arrang, J.-M.; Hüls, A.; Schunack, W.; Ganellin, C.R.; Optimization of 4-(3-(phenoxy)propyl)-1H-imidazoles leading to ciproxifan, a novel potent histamine H3-receptor antagonist. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.120.
【3】 Imidazole derivs. as histamine receptor H3 (ant)agonists. EP 0760811; FR 2732017; JP 1998501001; WO 9629315 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIIII)	27427	cyclopropyl(4-fluorophenyl)methanone	772-31-6	C₁₀H₉FO	详情	详情
(I)	27420	Urocanic acid; (E)-3-(1H-imidazol-4-yl)-2-propenoic acid	104-98-3	C₆H₆N₂O₂	详情	详情
(II)	27421	3-(1H-imidazol-4-yl)propionic acid		C₆H₈N₂O₂	详情	详情
(III)	27422	ethyl 3-(1H-imidazol-4-yl)propanoate		C₈H₁₂N₂O₂	详情	详情
(IV)	27423	ethyl 3-(1-trityl-1H-imidazol-4-yl)propanoate		C₂₇H₂₆N₂O₂	详情	详情
(V)	27424	3-(1-trityl-1H-imidazol-4-yl)-1-propanol		C₂₅H₂₄N₂O	详情	详情
(VI)	27425	cyclopropyl(4-hydroxyphenyl)methanone		C₁₀H₁₀O₂	详情	详情
(VII)	27426	cyclopropyl[4-[3-(1-trityl-1H-imidazol-4-yl)propoxy]phenyl]methanone		C₃₅H₃₂N₂O₂	详情	详情

Extended Information