Potassium Hydroxide → HCID 178463574, compound

Participants

Reaction Conditions

Reaction Steps

A solution of [(S)-1-(7-bromo-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine (300 mg, 0.56 mmol), tris(dibenzylideneacetone)dipalladium (0) (10 mg, 11 μmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (19 mg, 45 μmol), potassium hydroxide (94 mg, 1.6 mmol) in dioxane (3 mL), and water (2 mL) in a sealed tube were degassed by bubbling argon through the solution then heated by microwave at 150° C. for 30 min. Further portions of tris(dibenzylideneacetone)dipalladium (0) (30 mg, 33 μmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (57 mg, 135 μmol) were added and the mixture heated by microwave at 180° C. for 1 hour. The reaction mixture was diluted with water and extracted with EtOAc (3×10 mL). The combined organic fractions were washed with brine, dried (MgSO4), concentrated in vacuo. The product was purified by prep HPLC (C18 phenomonix column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient). The product was dissolved in HCl in methanol (1.25 M, 3 mL) and the reaction mixture stirred at RT for 10 min before being concentrated in vacuo. The product was purified by prep HPLC (C18 phenomonix column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient) to give 327 as a white solid (15 mg, 7%). 1H NMR 400 MHz δ (d6-DMSO): 9.53-9.38 (1H, m), 8.10-7.99 (2H, m), 7.82-7.69 (1H, m), 7.62-7.27 (5H, m), 7.10-6.93 (2H, m), 5.37-5.17 (1H, m), 1.43 (3H, d, J=7.0 Hz), LCMS (Method K): RT=2.55 min, [M+H]+=390

Provenance & Evidence