Lithium diisopropylamide → HCID 89485583, compound

Participants

Reaction Steps

A solution of 4-methyl-6-(thiazol-5-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)pyridin-2-amine (380 mg, 1.13 mmol) in 10 mL THF was cooled to −78° C., then LDA (2.5 mmol, freshly prepared) was added and the resulting mixture was stirred at the same temperature for 30 min. Then a solution of methyl 3-oxo-2,3-dihydro-1H-indene-5-carboxylate (1.13 mmol) in THF (3 mL) was added and the reaction was warmed to rt over a period of 4 h, then stirred for an additional 15 h at rt. The reaction was quenched by addition of saturated aqueous NH4Cl (10 mL) and the resulting mixture was extracted with EtOAc (2×20 mL). The combined organic phases were dried (MgSO4), filtered and concentrated, and the residue was purified by silica gel chromatography to afford racemic methyl 3-hydroxy-3-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-2,3-dihydro-1H-indene-5-carboxylate, which was resolved by chiral SFC (Column: Chiralcel OD-H 150×4.6 mm I.D., 5 um; Mobile phase: ethanol (0.05% DEA) in CO2 from 5% to 40%; Flow rate: 2.35 mL/min; Wavelength: 220 nm) to give each enantiomer. MS ESI calcd for C26H21F3N4O3S [M+H]+ 527, found 527.

Provenance & Evidence