反应详情

温度

80 °C

2-((6-Chloro-4-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)amino)isonicotinonitrile (50.0 mg, 0.159 mmol, 1.00 equiv), 3,3-difluoroazetidine hydrochloride (44.3 mg, 0.318 mmol, 2.00 equiv), sodium tert-butoxide (94.4 mg, 0.953 mmol, 6.00 equiv), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (7.56 mg, 0.0159 mmol, 0.100 equiv), and chloro-(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II)-methyl-t-butyl ether adduct (13.0 mg, 0.0159 mmol, 0.100 equiv) were added to a 2-dram vial. After purging the vial with nitrogen, dry tetrahydrofuran (1.50 mL) was added and the reaction mixture was left stirring at 80° C. for 14 h. The reaction mixture was then filtered over Celite washing with ethyl acetate (3×3 mL) and concentrated to dryness. Purification by reverse phase column chromatography (30:70 water/acetonitrile with 0.1% ammonium hydroxide) gave the desired product as a white solid (3.8 mg, 6.4% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.87 (s, 1H), 8.42 (d, J=5.1 Hz, 1H), 8.26 (s, 1H), 7.21 (dd, J=5.2, 2.0 Hz, 1H), 6.88 (s, 1H), 6.04 (s, 1H), 4.49-4.26 (m, 4H), 4.02-3.86 (m, 2H), 3.52-3.35 (m, 2H), 2.76-2.58 (m, 1H), 1.73-1.59 (m, 4H).

1. customAfter purging the vial with nitrogen, dry tetrahydrofuran (1.50 mL)
2. additionwas added
3. waitthe reaction mixture was left
4. filtrationThe reaction mixture was then filtered over Celite
5. washwashing with ethyl acetate (3×3 mL)
6. concentrationconcentrated to dryness
7. customPurification by reverse phase column chromatography (30:70 water/acetonitrile with 0.1% ammonium hydroxide)