Diisopropylethylamine → N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (200 mg, 0.97 mmol)[prepared according to Preparation 5], 1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxylic acid (339 mg, 0.97 mmol) and N,N-diisopropylethylamine (0.85 ml, 4.87 mmol) in dichloromethane (4.873 ml) at 25° C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (501 mg, 1.07 mmol) in one portion. The solution was stirred at 25° C. for 1 h and was then dry loaded onto silica and purified via column chromatography (silica, 30-70% EtOAc in hexanes) yielding N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide (522 mg, 0.93 mmol, 95% yield) as a white foam: LCMS (ES) m/e 536 (M+H)+.

Provenance & Evidence