3-Aminopyridine → HCID 89650076, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 4-chloro-6-(3-ethylureido)nicotinate, i (1.0 g, 3.70 mmol), in 1,4-dioxane (25 mL) was added 3-aminopyridine (0.435 g, 4.81 mmol) followed by Cs2CO3 (1.80 g, 5.55 mmol). The resulting solution was purged with nitrogen for 15 min followed by addition of Pd(OAc)2 (0.025 g, 0.11 mmol) and Xantphos (0.13 g, 0.22 mmol). The reaction mixture was again purged with nitrogen for 15 min and then heated at 80° C. overnight. The reaction mixture was cooled to room temperature, filtered through a celite bed, and the bed washed with EtOAc. The combined filtrate was concentrated under reduced pressure. Water was added to the residue and the mixture extracted with EtOAc (3×50 mL). The combined organic phase was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product thus obtained was triturated with a mixture of 10% MeOH-Et2O to obtain compound ii as an off-white solid (0.80 g, 66%). 1H NMR (DMSO-d6, 400 MHz): δ 9.62 (s, 1H), 9.17 (s, 1H), 8.63 (s, 1H), 8.56 (d, J=2.4 Hz, 1H), 8.41 (d, J=4.4 Hz, 1H), 7.77 (m, 1H), 7.75 (br s, 1H), 7.48 (m, 1H), 7.20 (s, 1H), 4.32 (q, J=6.8 Hz, 2H), 3.11 (q, J=7.20 Hz, 2H), 1.33 (t, J=6.8 Hz, 3H) and 1.03 (t, J=7.20 Hz, 3H). [M+H]+ m/z=330.12.

Provenance & Evidence