Cesium carbonate → 3-{7-[(5-bromopyridin-2-yl)oxy]-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl}-4-hydroxy-1-(isobutylamino)quinolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of the product of Example 321C (40.0 mg, 0.09 mmol), cesium carbonate (112 mg, 0.34 mmol), and 2,5-dibromopyridine (40.0 mg, 0.17 mmol) in dimethylsulfoxide (1.2 mL) was stirred while heating at 110° C. in a microwave reactor for 20 minutes. After cooling to 25° C., the purple mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with an additional portion of ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography on silica gel eluting with a step gradient (0-100%) of dichloromethane in hexanes to give the title compound as an off-white solid (34.0 mg, 63%). MS (ESI−) m/z 582 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 1.05 (d, J=6.62 Hz, 6 H) 1.93 (m, 1 H) 2.73 (m, 2 H) 6.35 (m, 1 H) 7.19 (d, J=8.82 Hz, 1 H) 7.45 (m, 1 H) 7.61 (dd, J=8.82, 2.57 Hz, 1 H) 7.77 (m, 2 H) 7.94 (m, 2 H) 8.13 (dd, J=8.82, 2.57 Hz, 1 H) 8.19 (m, 1 H) 8.31 (d, J=2.21 Hz, 1 H).

Provenance & Evidence