1-Bromo-3-chloropropane → 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Participants

Reaction Steps

To a solution of 1-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (278 mg, 0.783 mmol) in DMSO (4.0 mL) was added 3-bromo-1-chloropropane (1.23 g, 7.83 mmol) and Cs2CO3 (765 mg, 2.35 mmol), and the reaction was stirred at ambient temperature for 18 h. The reaction mixture was diluted with H2O (25 mL) and extracted with EtOAc (3×25 mL). The extracts were washed with brine (25 mL), dried over Na2SO4, and concentrated. Flash chromatography (silica gel, CH2Cl2/MeOH, 100:1) yielded the intermediate 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one. To a solution of 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (78 mg, 0.18 mmol) in DMF (1.0 mL) was added K2CO3 (0.12 g, 0.90 mmol), pyrrolidine (130 mg, 1.8 mmol) and KI (30 mg, 0.18 mmol), and the reaction was heated to 50° C. for 18 h. The reaction mixture was cooled and diluted with H2O (25 mL). The resulting solids were collected by filtration and washed with H2O (10 mL). The collected solid was dissolved in EtOAc (20 mL) and washed with brine (10 mL). The washed organic solution was dried over Na2SO4, filtered and concentrated to provide the title compound (77 mg, 91%): 1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.77-7.74 (m, 5H), 7.60-7.42 (m, 3H), 6.92 (d, J=2.0 Hz, 1H), 6.53-6.51 (m, 1H), 4.51 (t, J=7.0 Hz, 2H), 2.48-2.44 (m, 6H), 2.16-2.12 (m, 2H), 1.79-1.77 (m, 4H).

Provenance & Evidence