Dimethylformamide → N-(3-fluoro-4-(isoquinolin-5-yl)phenyl)-1-((S)-2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Participants

Reaction Steps

3-fluoro-4-(isoquinolin-5-yl)benzenamine (309.9 mg, 1301 μmol) and (S)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (359 mg, 1301 μmol) were suspended in DCM (6.5 ml) and DMF (0.65 ml) and hatu (579 mg, 1523 μmol) was added. The reaction was stirred under nitrogen for 5 days, and then filtered. The solid was washed with DCM, and the filtrate was concentrated and purified on silica gel (50:1->40:1->30:1->10:1 DCM/MeOH. The fractions with product were collected, concentrated, treated with MeOH and filtered. The solid was washed with MeOH, collected, and dried under high vacuum to afford the desired N-(3-fluoro-4-(isoquinolin-5-yl)phenyl)-1-((S)-2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (216.0 mg, 435.0 mmol, 33% yield). MS (ESI pos. ion) m/z: 497 (MH+). Calc'd exact mass for C29H25FN4O3: 496. 1H NMR (400 MHz, CDCl3) δ 10.93 (s, 1H), 9.30 (s, 1H), 8.49 (d, J=6.0 Hz, 1H), 8.01 (dd, J=7.0 Hz, 3.0 Hz, 1H), 7.87 (dd, J=12.0 Hz, 2.0 Hz, 1H), 7.71-7.64 (m, 2H), 7.59-7.52 (m, 3H), 7.48 (d, J=8.0 Hz, 1H), 7.42-7.34 (m, 3H), 7.31 (d, J=8.0 Hz, 1H), 4.00-3.83 (m, 2H), 3.72 (dd, J=15.0 Hz, 3.0 Hz, 1H), 2.89 (s, 3H), 1.29-1.24 (m, 1H), 1.11 (d, J=6.0 Hz, 3H).

Provenance & Evidence