Hydrochloric Acid → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

A vial was charged with the title compound from Example 236 Step C (60.0 mg, 0.098 mmol), 4-trifluoromethylphenyl boronic acid (24.2 mg, 0.127 mmol), and trans-dichlorobis(triphenylphosphine) palladium (II) (6.9 mg, 0.010 mmol). Acetonitrile (0.400 mL) and sodium carbonate (0.244 mL, 1.0 M aqueous, 0.244 mmol) were added, and the mixture was degassed with nitrogen. The vial was then capped and placed in a pre-heated oil bath (70° C.). After 15 h, the mixture was diluted with water and DCM and the organic phase was filtered through a short pad of silica gel and Celite with DCM, then was concentrated in vacuo: LCMS m/z 610.4 [M+H]+. To a solution of the unpurified Suzuki product in 1,4-dioxane (2.0 mL) was added lithium hydroxide (1.0 mL, 2.0 M in water, 2.00 mmol), and the resulting mixture was stirred at 50° C. After 1 h, the reaction mixture was rendered acidic by addition of aqueous hydrochloric acid, then was diluted with 1,4-dioxane and passed through a 0.45 micron syringe filter. Purification by reverse phase HPLC (60 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 582.4 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.34 (s, 1H), 8.20 (t, J=8.0 Hz, 1H), 7.82-7.73 (m, 6H), 7.50 (d, J=8.0 Hz, 2H), 7.44-7.34 (m, 4H), 6.99 (d, J=8.0 Hz, 2H), 2.97-2.93 (m, 2H), 2.78-2.74 (m, 2H).

Provenance & Evidence