Lithium diisopropylamide → HCID 131731735, compound

Participants

Reaction Steps

To a solution of 4-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine (600 mg, 1.78 mmol) in THF (5.9 mL) under argon at −78° C. was slowly added lithium diisopropylamide (2.0 M in THF, 2.68 mL, 5.35 mmol), and the resulting mixture was stirred for 30 minutes at that temperature. A solution of methyl 3-fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (496 mg, 2.230 mmol) in THF (2 mL) was added, and the reaction mixture was allowed to warm to rt over 2 h. After an additional 12 h, the reaction was quenched with methanol (10 mL) and concentrated under reduced pressure. Reverse-phase HPLC (C18 column, water-acetonitrile, TFA modifier) afforded (rac)-methyl 3-fluoro-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, trifluoroacetate salt (355.1 mg, 0.528 mmol, 30% yield) as a yellow solid. MS ESI calcd for C27H22F4N4O3S [M+H]+ 559, found 559. 1H NMR (500 MHz, DMSO) δ 10.22 (s, 1H), 8.65 (s, 1H), 8.48 (d, J=5.2 Hz, 1H), 8.26 (s, 1H), 7.69 (d, J=7.4 Hz, 1H), 7.37 (s, 1H), 7.21 (d, J=5.2 Hz, 1H), 7.14-7.06 (m, 2H), 3.82 (s, 3H), 2.89-2.77 (m, 2H), 2.41-2.32 (m, 1H), 2.30 (s, 3H), 2.13-2.06 (m, 1H), 2.00-1.85 (m, 2H) ppm.

Provenance & Evidence