Exquisite Synthesis of a Designed PAR-1 Antagonist.

The synthesis of a designed, sterically congested geminal dimethyl-bearing PAR-1 antagonist was achieved by a route of ten steps, with the oxidation of an electron-rich benzaldehyde, the construction of a tertiary alkyl azide, and the selective hydrogenolysis of a 1,5-fused tetrazole to generate the cyclic amidine with Raney-Ni being the key steps. The selective hydrogenolysis of 1,5-fused tetrazole to generate the cyclic amidine with Raney-Ni was discovered and may be generally used for the synthesis of structurally unusual cyclic amidines. Several unsuccessful attempts to construct the desired geminal dimethyl-bearing cyclic amidine were also discussed. [ABSTRACT FROM AUTHOR]