Kiyotaka Oyama

Position of methylation of 2,3-diaminopyridine and 3-amino-2-methyl-aminopyridine

Methylation of 3-amino-2-methylaminopyridine (III) with methyl iodide takes place exclusively at the 3-amino-group, unlike the cases of 2-methylaminopyridine and 3-aminopyridine where only ring methylation occurs. The position of methylation of 2,3-diaminopyridine (V) is solvent-dependent, with the ratio of ring to 3-amino-group methylation varying from 7·3:1 in acetonitrile to 1·1:1 in 4:1 2,2,2-trifluoroethanol-methanol. The diversion of methylation from the ring nitrogen atom to the 3-amino-group is attributed to a combination of steric and hydrogen-bonding effects.