Diisopropylethylamine → 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(4-fluorophenyl)methyl]ethyl}-5-methyl-2-thiophenecarboxamide

Participants

Reaction Steps

To a 50 mL round-bottomed flask was added 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylic acid (256 mg, 0.85 mmol), 2-[(2S)-2-amino-3-(4-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (1272 mg, 3.80 mmol) [prepared according to the procedure of Preparation 6 except substituting N-{[(1,1-dimethylethyl)oxy]carbonyl}-4-fluoro-L-phenylalanine (4.95 g, 17.5 mmol) for N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-(trifluoromethyl)-L-phenylalanine] and PyBrop (485 mg, 1.03 mmol) in Chloroform (8.5 mL). DIEA (750 μL, 4.29 mmol) was added and the reaction stirred overnight at room temperature. The mixture was adsorbed onto silica and purified via column chromatography (25-70% EtOAc/Hex) affording the title compound (319 mg, 0.50 mmol, 71%): LC-MS (ES) m/z=583 (M+H)+.

Provenance & Evidence