Triethylamine → HCID 86696482, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (2.8 g, 15 mmol), 3-bromo-6-fluoro-imidazo[1,2-b]pyridazine (2.16 g, 10 mmol), and triethylamine (5.58 ml, 40 mmol) in isopropyl alcohol (10 ml) was heated in a microwave at 140° C. for 30 min. The reaction mixture was concentrated and the residue was passed through a short column to afford the desired product (3.8 g). To a solution of above product (3.8 g) in DMF (40 ml) at 0° C. was added MeI (1.13 ml). The mixture was stirred at 0° C. for 5 min., NaH (800 mg, 60% oil dispersion, 20 mmol) was added portionwise. The reaction mixture was stirred at 0° C. for 5 min. and at rt for 30 min., then it was treated with water and diluted with EtOAc (250 ml). The mixture was washed with water (100 ml) and brine (100 ml). The aqueous layer was back extracted with EtOAc (2×50 ml). The combined EtOAc was dried (Na2SO4) and concentrated. The residue was subjected to ISCO (120 g column) to afford the titled compound (3.1 g). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.43 (s, 9H) 2.04-2.22 (m, 2H) 2.78 (s, 3H) 3.37 (dd, J=10.80, 7.28 Hz, 1H) 3.46 (dt, J=10.36, 8.05 Hz, 1H) 3.65-3.72 (m, 2H) 4.87 (br. s., 1H) 6.53 (d, J=9.70 Hz, 1H) 7.44 (s, 1H) 7.64 (d, J=9.70 Hz 1H). LRMS (ESI) m/z 396 and 398.1 [(M+H)]+, calc'd for C16H22BrN6O2: 396.29.

Provenance & Evidence