3-取代-1,2,3,9-四氢-4H咔唑-4-酮衍生物的合成

Synthesis of 3-Substituted-1, 2, 3, 9-tetrahydro-4H-carbazol-4-one Derivatives

为寻找新的5－HT3受体拮抗剂，以奥丹西隆（Ondansetron）为先导物，设计合成了6个未见报道的3－（2－烷基1H－苯并咪唑－1－基）甲基、3－（1H－苯并三唑－1－基）甲基和3－（1H－吲哚－3－基）甲基取代的1，2，3，9－四氢－4H－咔唑－4－酮衍生物（Ⅷa～d，Ⅸ和Ⅹ）。起始原料为间苯二酚，经过氢化、形成单苯腙、环合、甲基化得9－甲基－1，2，3，9－四氢－4H－咔唑－4酮（Ⅴ），再经过Mannich反应．形成盐酸盐，缩合反应制得目的物，对其中的甲基化反应，Man－nich反应等进行了条件优化。目的物均经红外光谱、核磁共振氢谱和质谱等确证。

On the basis of the structural features of the known highly selective 5-HT3 antagonists ondansetron, a series of 3- (2-alkyl- 1H-benzimidazolar-1- yl) methyl、3- (1H- benzotriazol- 1 - yl ) methyl and 3- (1H- indol-3- yl )methyl- 1, 2, 3, 9-tetrahydro-9-methyl- 4H-carbazol- 4-one derivatives (Ⅷa^d、Ⅸ and Ⅹ) were synthesized from 9- methyl- 1, 2, 3, 9- tetrahydro-4H-carbazol-4-one (Ⅴ) by Mannich reaction, salt forming reaction and condensation with appropriate benzimidazoles' benzotriazole and indole. Compound Ⅴ was prepared from resorcinol through catalytic hydrogenation, monophenylhydrazone forming reaction, cyclization and methylation. The improved processes of methylation and Mannich reaction were described. All the target compounds are thus far unreported and now identified by IR, 1HNMR and MS spectrum.