QF-2004B
Chemical Name: 2-[4-(6-Fluorobenzisoxazol-3-yl)piperidin-1-ylmethyl]-2,3,4,9-tetrahydro-1H-carbazol-4-one
项目整合开发状态: Preclinical
项目研究机构: Universidad de Santiago de Compostela (Originator)
合成路线:The reduction of 3,5-dimethoxybenzoic acid (I) first with Li in liquid NH3 and methanol,and then with LiAlH4 in THF gives 3,5-dimethoxy-1,4-dihydrobenzyl alcohol (II),which is cyclized with phenylhydrazine (III) in refluxing 4% sulfuric acid yielding 2-(hydroxymethyl)-1,2,3,4-tetrahydrocarbazol-4-one (IV).The reaction of (IV) with tosyl chloride in pyridine affords the corresponding tosylate (V),which is finally condensed with 4-(4-fluorobenzoyl)piperidine (VI) in N-methyl-2-pyrrolidone.
合成路线:The reduction of 3,5-dimethoxybenzoic acid (I) first with Li in liquid NH3 and methanol,and then with LiAlH4 in THF gives 3,5-dimethoxy-1,4-dihydrobenzyl alcohol (II),which is cyclized with phenylhydrazine (III) in refluxing 4% sulfuric acid yielding 2-(hydroxymethyl)-1,2,3,4-tetrahydrocarbazol-4-one (IV).The reaction of (IV) with tosyl chloride in pyridine affords the corresponding tosylate (V),which is finally condensed with 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (VI) in N-methyl-2-pyrrolidone.
📌 参考资料/链接：
参考文献标题:Butyrophenone analogues in the carbazole series: Synthesis and determination of affinities at D2 and 5-HT2A receptors
文献作者:Masaguer,C.F.; Formoso,E.; Ravi�? E.; Trist�? H.; Loza,M.I.; Rivas,E.; Fontenla,J.A.
参考来源:Bioorg Med Chem Lett 1998,8(24),3571
📄 详细内容
合成路线:The condensation of 3,5-dimethoxybenzoic acid (I) with 4-(4-fluorobenzoyl)piperidine (II) by means of DCC and HOBT in DMF gives the piperidide (III),which is reduced with LiAlH4 in THF to yield 1-(3,5-dimethoxybenzyl)-4-(4-fluorobenzoyl)piperidine (IV).The reduction of (IV) with Li in liquid ammonia affords the 1,4-dihydro derivative (V),which is finally cyclized with phenylhydrazine (VI) in refluxing aqueous sulfuric acid to provide the target tetrahydrocarbazolone.
合成路线:The condensation of 3,5-dimethoxybenzoic acid (I) with 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (II) by means of DCC and HOBT in DMF gives the piperidide (III),which is reduced with LiAlH4 in THF to yield 1-(3,5-dimethoxybenzyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (IV).The reduction of (IV) with Li in liquid ammonia affords the 1,4-dihydro derivative (V),which is finally cyclized with phenylhydrazine (VI) in refluxing aqueous sulfuric acid to provide the target tetrahydrocarbazolone.
参考文献标题:Butyrophenone analogues in the carbazole series as potential atypical antipsychotics: Synthesis and determination of affinities at D2,5-HT2A,5-HT2B and 5-HT2C receptors
文献作者:Masaguer,C.F.; Ravi�? E.; Fontenla,J.A.; Brea,J.; Tristan,H.; Loza,M.I.
参考来源:Eur J Med Chem 2000,35(1),83