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The discovery of MK-1220 is reported along with the development of a series of HCV NS3/4A protease inhibitors containing a P2 to P4 macrocyclic constraint with improved preclinical pharmacokinetics. Optimization of the P2 heterocycle substitution pattern as well as the P3 amino acid led to compounds with greatly improved plasma exposure following oral dosing in both rats and dogs while maintaining excellent enzyme potency and cellular activity. These studies led to the identification of MK-1220.

A new vinylamine equivalent, N-vinyloxazolone 3, has been prepared in three steps and shown to undergo Heck arylation with a variety of substrates. The Heck adducts thus obtained are then converted in one step and high yield to phenethylamine hydrochlorides. As a general synthetic method for preparation of substituted phenethylamines, use of this new reagent is shown to be superior to N-vinylphthalimide in number of steps, regiospecificity, and chemical yield

Two complementary methods for the preparation of α-substituted 1,2-benzenedimethanamines have been described. The N-substituted benzamide approach can be useful when the N-substituent on the phthalazinone is large; however, it does not have the versatility of the phthalazinone approach. In reducing the phthalazines with borane, a novel cleavage of a N-N bond has been encountered