Water → HCID 67441768, compound

Participants

Reaction Steps

To a solution of 107 (120 mg, 0.19 mmol) in DCM (20 mL) was added water (0.5 mL) and TFA (4 mL, 51.9 mmol). The reaction mixture was stirred at RT for 6 h, concentrated, diluted with ethyl acetate, and washed with 1N NaOH. The organic phase was collected and the aqueous phase was re-extracted with ethyl acetate. The combined organic layers (a lot of unsoluble material stayed on the walls of the separatory funnel which was dissolved in MeOH and combined with the organic layers) were concentrated. A 1N NaOH solution was added; the suspension was stirred for 30 min and the solid was collected by filtration. The crude product was purified by Biotage (SNAP 50 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 40/60 over 20 CV), to afford the title compound 108 (77 mg, 0.14 mmol, 76% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.77 (s, 1H), 8.55-8.51 (m, 2H), 8.36 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 7.81 (dd, J=8.0, 2.0 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.2 Hz, 1H), 7.20 (d, J=8.8 Hz, 1H), 6.65 (d, J=5.6 Hz, 1H), 6.60 (d, J=2.4 Hz, 1H), 4.52 (d, J=15.2 Hz, 1H), 4.45 (d, J=15.2 Hz, 1H), 4.15-3.65 (m, 214), 3.58 (t, J=8.8 Hz, 1H), 3.30-3.14 (m, 2H), 2.59-2.52 (m, 1H), 2.34-2.23 (m, 1H), 1.77-1.65 (m, 1H), 0.68-0.62 (m, 2H), 0.45-0.37 (m, 2H). MS (m/z): 533.6 (M+H).

Provenance & Evidence