trans-N,N'-dimethyl-1,2-cyclohexanediamine → methyl 6-methyl-3-(2H-1,2,3-triazol-2-yl)-2-pyridinecarboxylate

Participants

Reaction Steps

DMF (1.5 ml) was added to a mixture of methyl 3-iodo-6-methyl-2-pyridinecarboxylate D36 (100 mg), 1H-1,2,3-triazole (49.9 mg, 0.722 mmol), (1R,2R)—N,N′-dimethyl-1,2-cyclohexanediamine (10.27 mg, 0.072 mmol), CuI (3.44 mg, 0.018 mmol) and Cs2CO3 carbonate (235 mg, 0.722 mmol) in a microwave vial. The mixture was degassed via three vacuum/nitrogen cycles then irradiated in a single mode microwave reactor to 120° C. for 20 minutes. The mixture was irradiated in a single mode microwave reactor to 120° C. for a further 40 minutes. The reaction mixture was cooled and filtered washing the solids with EtOAc. The solids were dissolved in pH=3 buffer solution (5 ml); UPLC check of this aqueous solution showed it contained a considerable quantity of 6-methyl-3-(2H-1,2,3-triazol-2-yl)-2-pyridinecarboxylic acid. The aqueous phase was extracted repeatedly with DCM; the combined DCM extracts were diluted with MeOH (50 ml) and treated with TMS-diazomethane. The volatiles were evaporated to give a yellow residue that was purified by flash chromatography on silica gel (Biotage, SNAP 10 g column, 10%-50% EtOAc/Cy) to give the title compound D39 (38 mg) as a white solid. UPLC (Basic QC_POS—50-800): rt=0.57 minutes, peak observed: 219 (M+1). C10H10N4O2 requires 218. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (d, 1 H), 7.87 (s, 2 H), 7.44 (d, 1 H), 3.94 (s, 3 H), 2.71 (s, 3 H).

Provenance & Evidence