3H-IMidazo[4,5-c]pyridine-6-carboxylic acid, Methyl ester

114786-39-9

121-44-8

82523-07-7

The general procedure for the synthesis of methyl 3H-imidazo[4,5-c]pyridine-6-carboxylate from (S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester dihydrochloride (156.5 g, 0.62 mol) and triethylamine (445.0 g, 4.4 mol, 7.0 equiv) was as follows: selenium dioxide ( 158.2 g, 1.43 mol, 2.3 equiv) and polyphosphoric acid methyl ether (PPSE) (15.0 g) were added to carbon tetrachloride (CCl4) (1.5 L). After cooling to room temperature, the mixture was refluxed for 6 hours. After completion of the reaction, the solvent was removed under reduced pressure and the residue was suspended in methanol (1.5 L) and the pH was adjusted to 8 by addition of triethylamine. the brown solid was collected by filtration and washed well with methanol. The resulting brown solid (117.0 g) was recrystallized. The product was dissolved in hot N,N-dimethylformamide (DMF) (2 L) and hot filtered to remove the black selenium salt by-product. After cooling to room temperature, the target product crystallized as a yellow solid (51.3 g, 47% yield, 95% purity). The product was characterized as follows: 1H NMR (DMSO-d6): δ 13.20 (br s, 1H), 9.02 (s, 1H), 8.58 (s, 1H), 8.31 (s, 1H), 3.89 (s, 3H); LCMS: Rt = 1.33 min, [M + 1]+ = 178.1 m/z.