Sodium Carbonate → HCID 57584976, compound

Participants

Reaction Conditions

Reaction Steps

To a 25 mL round-bottomed flask was added N-(5-bromopyridin-3-yl)-4-fluorobenzenesulfonamide (0.15 g, 0.45 mmol), bis(pinacolato)diboron (0.17 g, 0.68 mmol, Aldrich, St. Louis. MO), potassium acetate (0.18 g, 1.8 mmol) and 1,4-dioxane (4.0 ml). The mixture was carefully evacuated and backfilled with N2 and then dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.033 g, 0.045 mmol, Strem, Newburyport, Mass.) was added. The mixture was carefully evacuated and backfilled with N2 again. The mixture was stirred at 90° C. for 19 hours and then allowed to cool to rt. To the mixture was added DMF (4.0 ml), N-(5-chlorothiazolo[5,4-b]pyridin-2-yl)acetamide (0.075 g, 0.33 mmol) and 2 M sodium carbonate (0.82 ml, 1.7 mmol). The mixture was carefully evacuated and backfilled with N2 and then trans-dichlorobis(triphenylphosphine)palladium (II) (0.023 g, 0.033 mmol, Strem) was added. The mixture was carefully evacuated and backfilled with N2 and then stirred at 90° C. for 18 h. The mixture was allowed to cool to room temperature and then poured into water (100 mL) and extracted with 25% iPrOH/CHCl3 (4×50 mL). The combined extracts were dried (Na2SO4) and concentrated. The residue was taken up in CH2Cl2/MeOH and concentrated onto silica. Purification by silica gel chromatography (3.0 to 10% MeOH (2 M in NH3)/CH2Cl2) afforded a brown solid. This was further purified by Prep-HPLC (Phenomenex Synergi 4u MAX-RP 80A 150×21.20 nm n, 00F-4337-P0, 2 to 100% CH3CN (0.1% TFA)/H2O (0.1% TFA) over 15 min then 100% CH3CN for 5 minutes at 20 ml/min) with the fractions containing suspected product concentrated to afford the title compound as a tan solid (0.012 g, 6.3% yield). MS (ESI pos. ion) m/z: 444 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.55 (s, 1H), 10.71 (s, 1H), 9.00 (d, J=1.8 Hz, 1H), 8.36 (d, J=2.5 Hz, 1H), 8.17-8.22 (m, 2H), 8.07 (d, J=8.6 Hz, 1H), 7.85-7.90 (m, 2H), 7.39-7.45 (m, 2H), 2.24 (s, 3H).

Provenance & Evidence