HCID 71143876, compound → HCID 71143880, compound

Participants

Reaction Conditions

Reaction Steps

In a 30 mL sealed cap glass vessel, tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (119 mg, 0.238 mmol), 1,3-dimethyl-5-(tributylstannyl)-1H-thieno[3,2-c]pyrazole (210 mg, 0.476 mmol) and tetrakis(triphenylphosphine)palladium(0) (137 mg, 0.119 mmol) were dissolved in toluene (5 mL). The cap was sealed and the reaction mixture was heated at 90° C. in an oil bath for 2 hours. The mixture was concentrated to give the intermediate, tert-butyl 6-(((3R,4R)-3-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(1-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate. The intermediate was dissolved in TFA (5 mL) and the reaction mixture was stirred for 1 hour. The mixture was concentrated, dissolved in DMSO (5 mL), and purified via preparatory HPLC eluting with a gradient of 15-50% ACN (0.035% TFA) and H2O (0.05% TFA). The pure fractions were combined, evaporated to a minimal volume, and lyophilized to give a TFA salt of the title compound as a white solid (65 mg, 68%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.79 (d, J=10.86 Hz, 1H), 2.04-2.26 (m, 1H), 3.55-3.68 (m, 2H), 3.80 (d, J=11.62 Hz, 1H), 3.89 (br s, 1H), 3.99 (s, 3H), 4.02-4.06 (m, 1H), 4.33 (td, J=8.27, 4.67 Hz, 1H), 4.45 (s, 2H), 7.40 (d, J=5.05 Hz, 1H), 7.74 (d, J=0.76 Hz, 1H), 7.96 (d, J=4.55 Hz, 2H), 8.65 (s, 1H), 9.28 (d, J=0.76 Hz, 1H). ESI-MS m/z [M+H]+ calc'd for C18H19FN6O2S, 403. found, 403.

Provenance & Evidence