Nitrogen → (R)-4-((R)-1-((3-cyclopropyl-6-(3-methylisothiazol-5-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a microwave tube equipped with a stirring bar, (R)-4-((R)-1-((3-cyclopropyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one: (133.6 mg, 0.324 mmol), 5-bromo-3-methylisothiazole (69.2 mg, 0.389 mmol), 1,2-dimethoxyethane (2 mL), 1 N Na2CO3 aqueous solution (0.97 mL, 0.97 mmol) were added, the mixture was bubbled N2 for 5 minutes before Pd(PPh3)4 (18.7 mg, 0.016 mmol) was added. The tube was sealed and heated in an oil bath at 100° C. for 2 hrs. DCM (200 mL) was added and the resulting mixture was washed with saturated NaHCO3 aqueous solution (20 mL×4), brine (20 mL×1), dried over anhydrous Na2SO4, filtered, removed solvents in vacuo. The resulting residue was passed a ISCO silica gel column (MeOH:DCM=5:95) to give white solids, 7.9 mg (yield 6.4%). 1H NMR (300 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.88 (s, 1H), 7.74 (s, 1H), 7.57 (s, 1H), 5.45-5.32 (m, 1H), 3.70 (m, 1H), 3.41 (t, J=9.1 Hz, 1H), 3.21 (dd, J=9.7, 6.6 Hz, 1H), 2.90-2.80 (m, 1H), 2.44 (s, 3H), 2.33 (d, J=8.8 Hz, 2H), 1.42 (d, J=6.1 Hz, 3H), 1.14 (m, 2H), 1.10-0.98 (m, 2H) ppm; MS (ESI+) m/z 384.88 (M+H).

Provenance & Evidence