Water → HCID 178480015, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-bromo-5-(2,4-difluorophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-benzimidazole and 5-bromo-6-(2,4-difluorophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-benzimidazole (0.0350 g, 0.0855 mmol) (mixture of isomers from step 6), cesium fluoride (0.0455 g, 0.299 mmol), and 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.0381 g, 0.0941 mmol) in 1-butanol (0.39 mL) and water (0.091 mL) was degassed with nitrogen for 5 min, treated with 4-(di-tert-butylphosphino)-N,N-dimethylaniline-dichloropalladium (2:1) (0.908 mg, 0.00128 mmol), degassed with nitrogen for 5 min, and heated at 100° C. for 2 h. The reaction mixture was poured into ethyl acetate (35 mL), washed with water and brine, dried with sodium sulfate, filtered, and concentrated to a crude oil. Purification by flash column chromatography (100% hexanes to 30% ethyl acetate [containing 5% MeOH]70% hexanes over 1 min and then 30% ethyl acetate [containing 5% MeOH]70% hexanes to 100% ethyl acetate [containing 5% MeOH] over 30 min) gave the desired product (33 mg, 63%) as a mixture of isomers. LCMS calculated for C31H36F2N5O4Si (M+H)+: m/z=608.2. found: 608.2.

Provenance & Evidence