Hydrochloric Acid → Trifluoroacetic acid

Participants

Reaction Steps

To a solution of the title compound from Example 12 Step F (24 mg, 0.035 mmol) in DCM (1 mL) were added DIEA (62 μL, 0.35 mmol) and acetyl chloride (8.3 mg, 0.104 mmol), and the resulting mixture was allowed to stir at room temperature. After 18 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 amide, which was used without further purification: LCMS m/z 606.9 [M+1-1]+. To a solution of the amide in dioxane (1.5 mL) was added lithium hydroxide (0.75 mL, 2N aqueous, 1.5 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 578.9 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.29 (s, 1H), 8.14 (d, J=8.0 Hz, 1H), 8.10 (t, J=8.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.56 (d, J=2.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.23-7.21 (m, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.15 (d, J=8.0 Hz, 1H), 5.16 (s, 2H), 4.52-4.49 (m, 1H), 3.91-3.87 (m, 1H), 3.12-3.07 (m, 1H), 2.77-2.70 (m, 1H), 2.58-2.53 (m, 1H), 2.27 (s, 3H), 2.01 (s, 3H), 1.78-1.72 (m, 2H), 1.59-1.51 (m, 1H), 1.44-1.35 (m, 1H).

Provenance & Evidence