4-(4-Fluorophenyl)-7-((4-formyl-1H-pyrazol-1-yl)methyl)quinoline-2-carboxamide → 7-({4-[Cyclopropyl(hydroxy)methyl]-1H-pyrazol-1-yl}methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a 0° C. solution of 4-(4-fluorophenyl)-7-[(4-formyl-1H-pyrazol-1-yl)methyl]quinoline-2-carboxamide (3-9, 36.0 mg, 0.0960 mmol, 1.0 equiv.) in anhydrous THF, under nitrogen was added dropwise 0.5 M cyclopropylmagnesium bromide in THF (0.769 mL, 0.385 mmol, 4.0 equiv.). The resulting mixture was stirred at 0° C. for 1 hour, quenched with sat. aqueous NH4Cl, extracted with ethyl acetate (3×5.0 mL), dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 7-({4-[cyclopropyl(hydroxy)methyl]-1H-pyrazol-1-yl}methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide (3-10, 25.0 mg, 62.4%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.228 (s, 1H); 8.084 (br s, 1H); 7.995 (s, 1H); 7.929 (d, J=8.81 Hz, 1H); 7.625 (s, 1 μl); 7.515 (s, 1H); 7.442-7.506 (m, 3H); 7.206-7.249 (m, 2H); 5.777 (br s, 1 μl); 5.526 (s, 2H); 4.044 (d, J=8.48 Hz, 1H); 1.185-1.258 (m, 1H); 0.599-0.638 (m, 2H); 0.331-0.454 (m, 2H). LRMS m/z (M+H)+ 417.2 found, 417.2 required.

Provenance & Evidence