8-Hydroxyquinoline → 1-(1-(2,2-Dimethoxyethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A suspension of 1-(2,2-dimethoxyethyl)-5-iodo-1H-indazole (458 mg, 1.38 mmol), 4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (330 mg, 1.38 mmol), Cs2CO3 (997 mg, 3.06 mmol), 8-hydroxyquinoline (42 mg, 0.29 mmol) and CuI (311 g, 163 mmol) in DMSO (5 mL) was evacuated for 30 minutes under high vacuum then backfilled with argon. The mixture was stirred under argon at 115° C. for 15 h and then allowed to cool. The mixture was diluted with 10% NH4OH in H2O (40 mL) and extracted with EtOAc (4×50 mL). The organics were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated to dryness. Purification by flash chromatography (silica gel, CH2Cl2/MeOH, 95:5) followed by a second purification by flash chromatography (silica gel, CH2Cl2/MeOH, 97.5:2.5) gave the title compound (482 mg, 79%) as a light brown solid: 1H NMR (500 MHz, CDCl3) δ 8.08 (s, 1H), 7.75-7.73 (m, 5H), 7.61 (d, J=8.9 Hz, 1H), 7.52 (d, J=7.1 Hz, 1H), 7.45 (dd, J=8.9, 1.8 Hz, 1H), 6.92 (d, J=1.8 Hz, 1H), 6.52 (dd, J=7.1, 1.9 Hz, 1H), 4.78 (t, J=5.3 Hz, 1H), 4.52 (d, J=5.3 Hz, 2H), 3.39 (s, 6H); ESI MS m/z 444 [M+H]+.

Provenance & Evidence