Dimethylformamide → HCID 54675650, compound

Participants

Reaction Steps

A DMF (3 mL) solution of the crude intermediate from Step C (77 mg, 0.135 mmol), copper (I) iodide (25.7 mg, 0.135 mmol), and N,N′-dimethylethylenediamine (14.3 mg, 0.162 mmol) was stirred at ambient temperature for 1 hour. The reaction mixture was diluted with EtOAc and washed with 10% aqueous NH4OH solution (2×), water (3×), and brine. The organic phase was JO dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by reverse phase HPLC using a water/acetonitrile (with 0.1% TFA) gradient. The isolated material was converted to the free base by suspending in EtOAc, washing with aqueous saturated NaHCO3 solution (2×) and brine. The solution was dried over anhydrous MgSO4, filtered, concentrated. The residue was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated compound as a racemic mixture. The enantiomers were separated on a ChiralPak IB column using 7% EtOH/heptane as eluent to give the indicated compound. Data is given for the faster eluting enantiomer. 1H NMR (500 MHz, DMSO-d6): δ (ppm) 11.23 (1H, s), 8.86 (1H, d, J=9.1 Hz), 8.07 (1H, d, J=2.1 Hz), 7.52 (1H, dd, J=9.0, 2.1 Hz), 7.37-7.25 (5H, m), 6.75 (2H, s), 3.30-3.20 (2H, m), 2.88-2.76 (2H, m), 1.79 (3H, s). m/z=487.1 (M+H).

Provenance & Evidence