Carbamate → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of the title compound from Example 148 Step C (170 mg, 0.246 mmol) in DCM (3 mL) was added TFA (1 mL). After 3 min, the reaction mixture was concentrated in vacuo to provide the crude TFA-salt, which was used without further purification: LCMS m/z 590.9 [M+1-1]+. A portion of the unpurified TFA salt (0.08 mmol) was dissolved in DCM (1 mL), and DIEA (130 μL, 0.74 mmol) was added, followed by methyl chloroformate (19 μL, 0.25 mmol). After 20 min, 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 unpurified carbamate, which was used without further purification: LCMS m/z 648.9 [M+H]+. To a solution of the carbamate in dioxane (2 mL) was added lithium hydroxide (1 mL, 2N aqueous, 2 mmol), and the mixture was stirred at 50° C. for 1 h, then at ambient temperature. After 15 h, the reaction mixture was rendered acidic by addition of HCl (2N aqueous), then was diluted with acetonitrile and purified by reverse phase HPLC (30 to 100% acetonitrile/water, both 0.1% v/v TFA) to provide the title compound: LCMS m/z 620.9 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.34 (s, 1H), 8.22 (t, J=8.0 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.95 (d, J=8.0 Hz, 1H), 7.88-7.86 (m, 2H), 7.54 (t, J=8.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.13 (d, J=8.0 Hz, 2H), 4.54 (s, 2H), 4.33-4.26 (m, 2H), 3.90-3.81 (m, 3H), 3.59 (s, 3H).

Provenance & Evidence