反应详情

To a solution of 4-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine (500 mg, 1.487 mmol) in THF (5.9 mL) under argon at −78° C. was added lithium diisopropylamide (2.0 M in tetrahydrofuran, 2.2 mL, 4.46 mmol), and the resulting mixture was stirred as such for 30 minutes. To this mixture was added a solution of methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (379 mg, 1.858 mmol) in THF (2 mL), and the reaction was then allowed to warm to rt over a period of 2 h. After stirring for an additional 14 h, the reaction was quenched with methanol (10 mL) and directly concentrated. Chromatography on silica gel (dichloromethane-methanol) afforded (rac)-methyl 5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate as a light brown solid (718.0 mg, 1.328 mmol, 89% yield). MS ESI calcd for C27H23F3N4O3S [M+H]+ 541, found 541. 1H NMR (500 MHz, DMSO) δ 10.20 (s, 1H), 8.63 (s, 1H), 8.48 (d, J=5.0 Hz, 1H), 8.23 (s, 1H), 7.74 (s, 1H), 7.69 (d, J=8.2 Hz, 1H), 7.36 (s, 1H), 7.23-7.17 (m, 2H), 7.09 (s, 1H), 6.63 (s, 1H), 3.82 (s, 3H), 2.92-2.85 (m, 2H), 2.33-2.30 (m, 4H), 2.15-2.09 (m, 1H), 2.02-1.88 (m, 2H) ppm.

1. stirringAfter stirring for an additional 14 h
2. customthe reaction was quenched with methanol (10 mL)
3. concentrationdirectly concentrated