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

Author:
Carr, Gregory R., Feron, James L., Johnson, Paul D., Roberts, Craig A., Rudge, David A., Simpson, Iain, Wrigley, Gail L.
Source:
Tetrahedron letters 2012 v.53 no.38 pp. 5049-5055
ISSN:
0040-4039
Subject:
acrylamides, chemical reactions, chemical structure, nitrogen
Abstract:
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.
Agid:
1099890