Chlorosuccinimide → 2-chloro-5-(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)-1-methyl-1H-pyrrole-3-carboxamide

Participants

Reaction Steps

A solution of 2-chloro-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 (125 mg, 0.22 mmol) and NCS (29 mg, 0.22 mmol) in tetrahydrofuran (2.2 ml) was stirred at 70° C. in a sealed tube. LCMS showed a 1:1 mixture of two chlorination products along with starting material. Additional NCS (29 mg, 0.22 mmol) was added and the solution stirred an additional 1 h where LCMS showed complete conversion to the two chlorination products. The resulting solution was partitioned between DCM-H2O and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated, dry loaded onto silica and purified by column chromatography (2% MeOH in DCM (1% NH4OH)) affording an inseparable mixture of the desired title compound along with a chloro-regioisomer: LCMS (ES) m/e 604, 606 (M, M+2)+.

Provenance & Evidence