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

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acid (200 mg, 0.74 mmol), N,N-diisopropylethylamine (0.64 ml, 3.69 mmol) and 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (284 mg, 0.74 mmol)[prepared according to Preparation 6] in DCM at 25° C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (414 mg, 0.886 mmol) in one portion. The solution stirred at 25° C. for 1 h and was then partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and the combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 50% EtOAc in hexanes) yielding 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-ethyl-2-thiophenecarboxamide (316 mg, 0.526 mmol, 71% yield) as a white foam: LCMS (ES) m/e 601, 603 (M, M+2)+.

Provenance & Evidence