Sodium Carbonate → HCID 49869929, compound

Participants

Reaction Conditions

Reaction Steps

[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (336 mg, 0.411 mmol) was added to a stirred solution of 4-(trifluoromethoxy)phenylboronic acid (1.27 g, 6.17 mmol), 2a (1.70 g, 4.11 mmol) and sodium carbonate (5.14 mL of a 2.0 M aqueous solution) in ethanol (32.0 mL) and toluene (8.0 mL). The resulting mixture was degassed and heated to 90° C. After 3 h, the reaction mixture was cooled to rt and filtered through a short column of Celite, eluting copiously with EtOH. The combined organics were concentrated in vacuo, and the crude residue was purified by column chromatography on silica gel (gradient elution, 1-9% MeOH/DCM as eluent), yielding a brown solid that was subsequently purified by reversed phase HPLC on YMC Pack Pro C18 phase (gradient elution; 10%-70% acetonitrile/water as eluent, 0.05% TFA modifier) to afford the title compound 2b. m/z (ES) 495 (MH)+. 1HNMR (500 MHz, CD3OD) δ 9.45 (s, 1H), 8.03 (d, 1H, J=1.7 Hz), 7.78 (d, 2H, J=3.3 Hz), 7.70 (d, 1H, J=0.3 Hz), 7.66 (dd, 1H, J=1.5, 3.5 Hz), 7.39 (d, 2H, J=1.7 Hz), 4.15 (m, 1H), 3.13 (m, 2H), 2.55 (d, 1H, J=2.3 Hz), 2.15 (d, 1H, 2.4 Hz), 1.60-1.90 (m, 6H), 1.23 (m, 6H). IC50=3.6 nM

Provenance & Evidence