Hydrochloric Acid → Trifluoroacetic acid

Participants

Reaction Steps

To a solution of the title compound from Example 12 Step F (48 mg, 0.071 mmol) in DCM (1 mL) were added DIEA (124 μL, 0.708 mmol) and dimethylcarbamyl chloride (20 μL, 0.213 mmol), and the resulting mixture was allowed to stir at room temperature. After 1.5 h, the reaction mixture was quenched by addition of sat aq NaHCO3 and the aqueous phase was extracted with DCM. The organic phase was separated and concentrated in vacuo to provide the crude urea, which was used without further purification: LCMS m/z 635.8 [M+H]+. To a solution of the urea in dioxane (2 mL) was added lithium hydroxide (1 mL, 2N aqueous, 2 mmol), and the mixture was stirred at 50° C. After 1 h, the reaction mixture was rendered acidic by addition of HCl (2N aqueous), then was diluted with acetonitrile and purified by reverse phase HPLC (40 to 100% acetonitrile/water, both 0.1% v/v TFA) to provide the title compound: LCMS m/z 607.8 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.31 (s, 1H), 8.15 (d, J=7.0 Hz, 1H), 8.11 (t, J=8.0 Hz, 1H), 7.70 (d, J=7.0 Hz, 1H), 7.57 (d, J=2.0 Hz, 1H), 7.34 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.24-7.22 (m, 1H), 7.17 (d, J=8.5 Hz, 1H), 5.17 (s, 2H), 3.65-3.63 (m, 2H), 2.79-2.77 (m, 2H), 2.75 (s, 6H), 2.69-2.64 (m, 1H), 2.28 (s, 3H), 1.75-1.72 (m, 2H), 1.61-1.52 (m, 2H).

Provenance & Evidence