反应详情

温度

25 °C

To a solution of 5-chloro-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (53 mg, 0.203 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (78 mg, 0.203 mmol) [prepared according to Preparation 6] and diisopropylethylamine (0.18 ml, 1.02 mmol) in DCM at 25° C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (95 mg, 0.203 mmol) in one portion. The solution stirred at 25° C. over 12 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, 40% EtOAc in hexanes) yielding 5-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide (106 mg, 0.129 mmol, 63.5% yield) as a clear oil; LCMS (ES) m/e 591, 593 (M, M+H)+.

1. customwas then partitioned between H2O-DCM
2. washThe aqueous phase was washed several times with DCM
3. dry with materialthe combined organic fractions were dried over Na2SO4
4. concentrationconcentrated
5. custompurified via column chromatography (silica, 40% EtOAc in hexanes)