A novel approach to functionalised 5,7,8,9-tetrahydropyrimido[4,5-b][1,4] diazepin-6-ones using intramolecular palladium-catalysed amidation

作者：Carr Gregory R; Feron James L; Johnson Paul D; Roberts Craig A; Rudge David A; Simpson Iain; Wrigley Gail L^*

来源：Tetrahedron Letters, 2012, 53(38): 5049-5055.

DOI：10.1016/j.tetlet.2012.03.125

• Palladium
• Amidation
• Bicyclic
• Pyrimidine
• Intramolecular

The development of a novel palladium-catalysed amidation approach towards 5,7,8,9-tetrahydropyrimido[4,5-b][1,4]diazepin-6-one templates is highlighted. The route proceeds through the reaction of an amino amide, generated by 1,4-addition of an amine to an acrylamide, with 5-bromo-2,4-dichloropyrimidine and final palladium-catalysed cyclisation to provide the functionalised scaffold in up to 60% isolated yield over three steps. The route offers efficiency advantages over the previously reported nitro-reduction cyclisation approach to these molecules. It also provides alternative means to introduce bulky alkyl substituents at the amide nitrogen. The application of this route in the synthesis of a variety of analogues is described.

• 出版日期2012-9-19