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

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• 作者：Gregory R. Carr ; James L. Feron ; Paul D. Johnson ; Craig A. Roberts ; David A. Rudge ; Iain Simpson ; Gail L. Wrigley
• 关键词：Palladium ; Amidation ; Bicyclic ; Pyrimidine ; Intramolecular
• 刊名：Tetrahedron Letters
• 出版年：2012
• 出版时间：19 September, 2012
• 年：2012
• 卷：53
• 期：38
• 页码：5049-5055
• 全文大小：829 K

文摘

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.