Automated generation of a dihydropyrimidine compound library using microwave-assisted processing
Automated generation of a dihydropyrimidine compound library using microwave-assisted processing
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DOI：
10.1038/nprot.2007.224
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发表时间：
2007-01-01
期刊：
影响因子：
14.8
通讯作者：
Kappe, C. Oliver
中科院分区：
文献类型：
--
作者：
Dallinger, Doris;Kappe, C. Oliver
在这里，我们报告了一个小的集中文库的12个不同功能化的二氢嘧啶（DHPM）衍生物通过一锅三组分Biginelli环缩合β -酮酯，醛和（硫）脲生成。通过在密封容器条件下使用全自动微波仪器（包括夹具和液体处理机）进行受控微波加热，与通常需要几个小时回流加热的传统加热方法相比，DHPM的顺序合成可以在更短的反应时间内完成（每一个DHPM衍生物10-20分钟）。固体产物要么在冷却时直接结晶，要么在加水后沉淀，只需要过滤隔离。这样，DHPM衍生物获得了高纯度，不需要通过重结晶或色谱进一步纯化。这可以归因于微波加热技术，其中较少的副产物形成经常被看到。这个12人DHPM文库的制备可以在大约9小时内完成。
Here we report the generation of a small focused library of 12 diversely functionalized dihydropyrimidine ( DHPM) derivatives via one-pot three-component Biginelli cyclocondensation of beta-ketoesters, aldehydes and ( thio) ureas. By applying controlled microwave heating under sealed vessel conditions using a fully automated microwave instrument including a gripper and liquid handler, the sequential synthesis of DHPMs can be performed in a shorter reaction time (10-20 min per one DHPM derivative) compared to conventional heating methods, which normally require several hours of reflux heating. The solid products either crystallize directly upon cooling or can be precipitated upon addition of water, requiring only filtration for isolation. In this way, the DHPM derivatives are obtained in high purity and no further purification by recrystallization or chromatography is necessary. This can be ascribed to the microwave heating technology where less side-product formation is often seen. The preparation of this 12-membered DHPM library can be carried out within similar to 9 h.