Synthesis of MAPA Reagents and 2-Alkyl(aryl)aminopyridines from 2-Bromopyridine Using the Goldberg Reaction

Abstract

A short and economical synthesis of various 2-methylaminopyidine amides (MAPA) from 2-bromopyridine has been developed using the catalytic Goldberg reaction. The effective catalyst was formed in situ by the reaction of CuI and 1,10-phenanthroline in a 1/1 ratio with a final loading of 0.5–3 mol%. The process affords high yields and can accommodate multigram-scale reactions. A modification of this method provides a new preparation of 2-N-substituted aminopyridines from various secondary N-alkyl(aryl)formamides and 2-bromopyridine. The intermediate aminopyridine formamide is cleaved in situ through methanolysis or hydrolysis to give 2-alkyl(aryl)aminopyridines in high yields.

Keywords

• <i>N</i>-methyl-<i>N</i>-(2-pyridyl)formamide
• 2-methylaminopyridine amides
• 2-alkyl(aryl)aminopyridines
• Goldberg reaction
• copper-catalyzed reactions
• cross-coupling reactions