巴格列酮的合成新工艺研究

Study on New Process of Synthesizing Balaglitazone

以邻氨基苯甲酰胺为起始原料,微波法合成中间体2-氯甲基-3-甲基-4-氧代-3,4-二氢喹唑啉(5);以对羟基苯甲醛和2,4-噻唑烷二酮进行Knoevenagel反应合成中间体5-[(4-羟基)苯亚甲基]噻唑烷二酮(8);然后8与5经醚化反应及催化氢化得到目标物巴格列酮。本路线操作简单、成本较低、条件温和、步骤少,适合工业化生产,总收率为48%。

2-Chloromethyl-3-methyl-3H-quinazolin-4-one(5) was prepared using 2-amino-benzamide as raw material through microwave-assisted method.The intermediates 5-(4-hydroxy-benzylidene)-thiazolidine-2,4-dione(8) was synthesized from4-hydroxy-benzaldehyde with thiazolidine-2,4-dione by Knoevenagel reaction.Balaglitazone was synthesized from intermediates 5 with 8 by etherification and catalytic hydrogenation with an overall yield of about 48%.This improved method can be used in industrial manufacturing with the advantage of simple purifying operation,low cost and mild condition.