反应详情

Methylmagnesium bromide solution (3 M in ether, 20 mL) is added to a solution of 5-(6-formyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide (5.0 g 11.7 mmol) in THF (400 mL) at 0° C. The mixture is stirred at that temperature for 3 h before the reaction is then quenched with saturated aqueous NH4Cl. The product is extracted with EtOAc (3×40 mL) and the combined organic layers are washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue is purified semi-prep HPLC (C18; 30-100% I/H2O with 0.1% TFA) to give the title compound as a racemate. MS (ESI) m/z 441.1 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.62 (s, 1H), 8.36 (d, J=8.84 Hz, 1H), 8.06 (s, 1H), 7.95 (d, J=3.79 Hz, 1H), 7.90 (d, J=8.08 Hz, 1H), 7.58 (t, J=7.83 Hz, 1H), 7.43 (d, J=2.27 Hz, 2H), 7.12 (dd, J=8.97, 2.40 Hz, 1H), 7.09 (s, 1H), 6.75 (d, J=3.79 Hz, 1H), 4.75 (d, J=6.57 Hz, 1H), 1.45 (d, J=6.57 Hz, 3H).

1. customis then quenched with saturated aqueous NH4Cl
2. extractionThe product is extracted with EtOAc (3×40 mL)
3. washthe combined organic layers are washed with brine
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue is purified semi-prep HPLC (C18; 30-100% I/H2O with 0.1% TFA)