Sodium Carbonate → 1-(((5S,7S)-7-methyl-3-((4-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Participants

Reaction Steps

To a microwave vial was added 1-(((5S,7S)-3-((4-bromopyridin-2-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (100 mg, 0.202 mmol), sodium carbonate (64.3 mg, 0.607 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (63.1 mg, 0.303 mmol), and PdCl2(dpV) (14.80 mg, 0.020 mmol) in 1,4-Dioxane (3.0 mL) and Water (1.000 mL). The mixture was subjected to the microwave at 120° C. for 20 minutes. The mixture was diluted with saturated NaHCO3 and extracted with DCM (3×). The combined DCM extracts were passed through a phase separator and concentrated. The residue was purified via reverse HPLC (Waters Sunfire 30×150 mm Acetonitrile:Water TFA 20-60%, 50 mL/min, 15 min). The product was free based with PL-HCO3 resin SPE to yield 1-(((5S,7S)-7-methyl-3-((4-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (99 mg, 94%). 1H NMR (400 MHz, DMSO-d6) δ 8.50-8.61 (m, 3H), 8.38 (s, 1H), 8.22 (s, 1H), 7.85 (d, J=8.28 Hz, 1H), 7.73-7.82 (m, 2H), 7.61 (dd, J=8.28, 1.25 Hz, 1H), 4.53 (dd, J=21.83, 16.31 Hz, 2H), 4.07-4.20 (m, 2H), 3.93 (s, 3H), 3.28 (dd, J=19.07, 8.78 Hz, 2H), 1.97 (d, J=13.30 Hz, 1H), 1.79 (d, J=14.56 Hz, 1H), 1.52-1.73 (m, 3H), 1.25-1.49 (m, 3H), 1.05 (s, 3H). MS (m/z) 496.3 (M+H+).

Provenance & Evidence