GSK3抑制剂的合成

4-甲酰基-2E-丁烯酸乙酯(8)经醛基保护、与2-氨基吡啶反应成环、加压氨化得到(11);5-氟-2-硝基苯甲醛(1)经醛基保护、Bartoli合成法制成吲哚、与乙醇胺反应并氢化、Boc保护、甲磺酰化、碱环合、与草酰氯甲醇钠反应制得(12);(11)与(12)对接、去保护、酰化得到目标化合物3-9-氟2-(哌啶-1-羰基)-1,2,3,4-四氢-1,4]-二氮杂卓艹并6,7,1-hi]吲哚基-7]-4-咪唑并1,2-a]吡啶基-3-吡咯-2,5-二酮.以化合物(1)为起始原料计算,共10步反应,总收率18%.

Synthesis of GSK3 Inhibitor

The intermediate(11)was prepared from(E)-ethyl 3-formylacrylate(8)via protection,cyclization and ammoniation under pressure;the key intermediate(12)was prepared by 5-fluoro-2-nitrobenzaldehyde(1)via protection,Bartoli reaction,reduction,protection with Boc2O,methanesulfonylation,cyclization,treatment with oxalyl dichloride and sodium methoxide;the compound 3-9-Fluoro-2-(piperidine-1-carbonyl)-1,2,3,4-tetrahydro-1,4 diazepino 6,7,1-hi indal-7-yl -4-imidazo 1,2-a pyridin-3-yl-pyrrole-2,5-dione was synthesized via cyclization with intermediates(11)and(12),and then deprotection,acylation with an overall yield of 18% after 10 steps combined starting from compound(1).