Nitrogen → (R)-4-((R)-1-((1-cyclopropyl-5-(2-(tetrahydro-2H-pyran-4-yl)thiazol-5-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a microwave tube equipped with a stirring bar, (R)-4-((R)-1-((1-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one (100 mg, 0.243 mmol), 5-bromo-2-(tetrahydro-2H-pyran-4-yl)thiazole (65.5 mg, 0.264 mmol), 1,2-dimethoxyethane (2 mL), 1 N Na2CO3 aqueous solution (0.60 mL, 0.60 mmol) were added, the mixture was bubbled N2 for 5 minutes before Pd(PPh3)4 (11.6 mg, 0.01 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 off-white solids, 57.5 mg (yield 52.3%). 1H NMR (300 MHz, DMSO-d6) δ 8.12 (s, 1H), 8.08 (s, 1H), 7.60 (s, 1H), 7.40 (d, J=1.2 Hz, 1H), 7.07 (d, J=1.3 Hz, 1H), 4.85 (p, J=5.9 Hz, 1H), 4.00-3.88 (m, 2H), 3.76-3.62 (m, 1H), 3.55-3.42 (m, 2H), 3.42-3.36 (m, 1H), 3.28-3.14 (m, 1H), 2.88-2.71 (m, 1H), 2.41-2.19 (m, 2H), 2.06-1.93 (m, 2H), 1.85-1.65 (m, 2H), 1.31 (d, J=6.0 Hz, 3H), 1.14-1.06 (m, 2H), 1.06-0.96 (m, 2H) ppm; MS (ESI+) m/z 453.09 (M+H).

Provenance & Evidence