Abstract: Carvedilol，a highly effective antihypertensive drug，not only is a third β-adrenergic receptor antagonist but also can be used to inhibit ?1-adrenoceptor. Recent synthetic routes of carvedilol differ from various starting materials. The synthesis methods of carvedilol are divided into two reaction types，whether the nitrogen atom contains protecting group or not. Here we show the two different reaction types that introducing a protecting group such as benzyl by intermolecular nucleophilic reaction and forming a cyclic amide structure by intramolecular reaction to protect the nitrogen atom. In this paper，we also discovered that using the 4-hydroxy carbonzole as starting material can effectively avoid various byproducts，which significantly improves the yield of carvedilol.

Key words: carvedilol, hypertension, synthesis, global optimization

摘要： 卡维地洛是一种治疗高血压病的第三代β受体阻滞剂，同时兼具有选择性?1受体阻滞剂作用，是一种大品种的高效抗高血压药物，但是在现有的制备方法中卡维地洛的收率较低。目前国内外对卡维地洛的合成报道较多，但是对卡维地洛制备工艺路线的综述鲜有报道。根据起始原料的不同可以分为多种合成路线，本文着重分析了氮上含保护基团的反应和氮上不含保护基团的两种反应类型，保护氮的方式可通过分子间亲核取代反应引入苄基等保护基团和通过分子内反应形成环酰胺结构保护氮。通过分析及优化，指出以中间体4-羟基咔唑作为起始原料的反应，可以有效避免多种副产物的产生，从而能够显著提高卡维地洛的收率。

关键词: 卡维地洛, 高血压, 合成, 整体优化