Cesium carbonate → HCID 68183169, compound

Participants

Reaction Conditions

Reaction Steps

In a 20 mL microwave vial a mixture of 3-bromo-4-(4-chlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (493.0 mg, 1.152 mmol, single enantiomer of unknown configuration), dicesium carbonate (1.13 g, 3.46 mmol), 1,4-dioxane (4.0 mL, 51 mmol), water (1.41 mL, 78.4 mmol) and vinylboronic acid dibutyl ester (381 uL, 1.73 mmol) was degassed by bubbling argon through the mixture for 10 min. Tetrakis(triphenylphosphine)-palladium(0) (66.6 mg, 0.0576 mmol) was added, the vial was sealed, and the r×n was heated at 100° C. for 15 h. The reaction was cooled to rt, diluted with water, and extracted with EA twice. The combined organics were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude material was (dry loaded on Celite and purified using column chromatography on silica gel (40 g ISCO column, gradient 100% hexanes to 100% EA over 60 minutes) to give the title compound (264 mg yellow solid, 61%). Final purification of 50 mg of this material by HPLC gave 30 mg pure product as a white solid. LCMS: (FA) ES+ 375, 377. 1H NMR (400 MHz, DMSO) δ 7.48 (d, J=4.6 Hz, 1H), 7.42-7.32 (m, 2H), 7.09-7.00 (m, 2H), 6.38 (dd, J=18.0, 11.8 Hz, 1H), 5.37 (dd, J=18.0, 1.7 Hz, 1H), 5.17 (dd, J=11.8, 1.6 Hz, 1H), 4.36 (d, J=4.3 Hz, 1H), 3.90 (dd, J=12.8, 5.0 Hz, 1H), 3.76-3.69 (m, 4H), 3.29 (dd, J=11.7, 5.1 Hz, 1H), 3.05-3.00 (m, 2H), 2.99-2.92 (m, 2H).

Provenance & Evidence