HCID 71143910, compound → HCID 71143937, compound

Participants

Reaction Conditions

Reaction Steps

In a 30 mL sealed cap glass tube, 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 (100 mg, 0.200 mmol), 2,3-dimethyl-5-(tributylstannyl)-2H-thieno[3,2-c]pyrazole (176 mg, 0.399 mmol) and tetrakis(triphenylphosphine)palladium(0) (115 mg, 0.100 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)-4-(2,3-dimethyl-2H-thieno[3,2-c]pyrazol-5-yl)-7-fluoro-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 2 hours. The mixture was concentrated, dissolved in DMSO (5 mL), and purified via preparatory HPLC eluting with a gradient of 10-60% 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, 61%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.80 (d, J=12.38 Hz, 1H), 1.96-2.25 (m, 1H), 2.46 (s, 3H), 3.55-3.71 (m, 1H), 3.82 (d, J=11.87 Hz, 1H), 3.92 (s, 3H), 4.05 (d, J=11.12 Hz, 3H), 4.28-4.38 (m, 1H), 4.40-4.51 (m, 2H), 7.37 (d, J=4.80 Hz, 1H), 7.96 (d, J=4.80 Hz, 3H), 8.63 (s, 1H), 9.26 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C19H21FN6O2S, 417. found, 417.

Provenance & Evidence