Chemical Name: 1-(4-Fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]butan-1-ol hydrochloride
CAS No. 99931-60-9
项目整合开发状态: Phase II
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The reaction of 2-chloro-5-fluoro-4-(methylsulfanyl)pyrimidine (I) with N-carbethoxypiperazine (II) yields (III),which upon treatment with Raney Nickel affords ethyl 4-(5-fluoro-2-pyrimidinyl)-1-piperazinecarboxylate (IV).Hydrolysis and decarboxylation of (IV) generates 5-fluoro-2-(1-piperazinyl)pyrimidine (V).The reaction of (V) with the alpha-chloroketal (VI) generates the butyrophenone derivative (VII).Sodium borohydride reduction of (VII) and treatment with ethanolic hydrochloric acid yields BMY-14802-1.
📄 详细内容
合成路线:The reaction of 2-chloro-5-fluoro-4-(methylsulfanyl)pyrimidine (I) with N-carbethoxypiperazine (II) yields (III),which upon treatment with Raney Nickel affords ethyl 4-(5-fluoro-2-pyrimidinyl)-1-piperazinecarboxylate (IV).Hydrolysis and decarboxylation of (IV) generates 5-fluoro-2-(1-piperazinyl)pyrimidine (V).The reaction of (V) with the alpha-chloroketal (VI) generates the butyrophenone derivative (VII).Sodium borohydride reduction of (VII) and treatment with ethanolic hydrochloric acid yields BMY-14802-1.
参考文献标题:BMY-14802-1
文献作者:Yocca,F.D.; Yevich,J.P.; New,J.S.
参考来源:Drugs Fut 1987,12(8),752
合成路线: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.
参考文献标题:Fluorine-18 labeled BMY 14802: Synthesis and anatomical distribution in rodents
文献作者: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.
参考来源:J Label Compd Radiopharm 1993,32501
合成路线: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.
参考文献标题:Synthesis and PET studies of fluorine-18-BMY-14802 - A potential antipsychotic drug
文献作者:Ding,Y.S.; Fowler,J.S.; Dewey,S.L.; Wolf,A.P.; Logan,J.; Gatley,S.J.; Volkow,N.D.; Shea,C.; Taylor,D.P.
参考来源:J Nucl Med 1993,34(2),246