A General Synthesis of Dihydronaphthyridinones with Aryl-Substituted Quaternary Benzylic Centers
John C Murray1, Colin R Rose1, John M Curto1
1Pfizer Worldwide Research, Development & Medicine, Groton, Connecticut 06340, United States.
Abstract:
A variety of 7,8-dihydro-1,6-naphthyridin-5(6H)-ones and 3,4-dihydro-2,7-naphthyridin-1(2H)-ones with quaternary centers and aryl substitutions at the benzylic carbon were synthesized with a new 3-step, 2-pot method. The first step is an SNAr using widely available 2- and 4-chloronicotinate esters and tertiary benzylic nitriles. The last two steps are a one-pot selective nitrile reduction in the presence of various heterocycles followed by a lactam ring closure of the free amine on the ester.
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