Potassium Phosphate, Tribasic → HCID 86727263, compound

Participants

Reaction Conditions

Reaction Steps

To a 30 mL sealed cap glass vessel containing tert-butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (200 mg, 0.401 mmol) and 2-(4-fluorothiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (137 mg, 0.601 mmol) dissolved in DME and water (4:1) was added tetrakis(triphenylphosphine)palladium(0) (105 mg, 0.401 mmol) and potassium phosphate, tribasic (212 mg, 1 mmol). The cap was sealed, and the reaction mixture was heated at 85° C. for 4 hours and then cooled to room temperature. The mixture was diluted with water and extracted with EtOAc (2×25 mL). The organic layers were combined, dried over sodium sulfate, and evaporated to give the intermediate, tert-butyl 6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)-7-fluoro-4-(4-fluorothiophen-2-yl)-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate. The intermediate was dissolved in TFA (5 mL) and stirred at room temperature for 2 hours. The mixture was evaporated and purified by preparative HPLC, eluting with a gradient of 15-50% ACN (0.035% TFA) and H2O (0.05% TFA). The pure fractions were combined, evaporated to minimal volume, and lyophilized to give a TFA salt of the title compound as a white solid (112 mg, 77%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29-1.54 (m, 2H), 1.60 (d, J=12.88 Hz, 2H), 1.66-1.81 (m, 2H), 1.83-1.99 (m, 2H), 3.81 (br s, 1H), 4.24 (br s, 1H), 4.45 (d, J=2.27 Hz, 2H), 7.14 (d, J=5.31 Hz, 1H), 7.31 (t, J=1.39 Hz, 1H), 7.79 (br s, 3H), 8.62 (s, 1H), 8.97 (d, J=1.77 Hz, 1H). ESI-MS m/z [M+H]+ calc'd for C17H18F2N4OS, 365. found, 365.

Provenance & Evidence