Ethanol → 2-(4-(5-cyanopyridin-3-yl)phenyl)-N-isobutyl-2-methylpropanamide

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Reaction Steps

N-isobutyl-2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanamide (example 23a) (14.86 g, 43.03 mmol), 5-bromonicotinonitrile (7.50 g, 40.98 mmol) and potassium carbonate (11.33 g, 81.96 mmol) were mixed in toluene (75 mL), ethanol (15 mL) and water (11.25 mL). The mixture was degassed for 30 minutes and Pd(PPh3)4 (950 mg, 0.82 mmol) was added. The reaction mixture was heated to reflux for 16 hr and cooled to room temperature then diluted with EtOAc/water, washed successively with water and brine, dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel (eluant 40% EtOAc in hexane) twice, then recrystallized from EtOAC/hexane and co-evaporated with ethanol to give 11.6 g of the product as a white solid in 88% yield. 1H NMR (400 MHz, DMSO-d6): δ 0.75 (d, 6H)), 1.48 (s, 6H), 1.70 (m, 1H), 2.85 (t, 2H), 7.45 (m, 3H), 7.8 (d, 2H), 8.65 (t, 1H), 9 (d, 1H), 9.2 (d, 1H). MS(M+H, 322).

Provenance & Evidence