Diisopropylethylamine → 5-(2-((S)-1-(2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-5-(1,3-dioxoisoindolin-2-yl)pyridin-3-yl)-2-fluorobenzamide

Participants

Reaction Conditions

Reaction Steps

2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid (13 mg, 0.045 mmol), (S)-5-(2-(1-amino-2-(3,5-difluorophenyl)ethyl)-5-(1,3-dioxoisoindolin-2-yl)pyridin-3-yl)-2-fluorobenzamide hydrochloride (30I, 25 mg, 0.045 mmol) and HATU (21 mg, 0.054 mmol) were dissolved in 10 mL DMF, cooled to 0° C., then N,N-diisopropylethylamine (0.032 mL, 0.18 mmol) was added dropwise. The reaction mixture was allowed to stir at 0° C. for 5 min, and then partitioned between EtOAc and 5% LiCl aqueous solution. The organic layer was separated, washed with NaHCO3 (sat'd aq.) and brine. After dried over MgSO4, it was filtered and concentrated. The residue was purified by RP-HPLC eluting with acetonitrile/H2O (with 0.1% TFA) to afford the title compound. 1H NMR (400 MHz, CD3OD): δ 8.87 (s, 1H), 7.98 (m, 2H), 7.88 (m, 2H), 7.76 (d, 1H), 7.54-7.30 (m, 2H), 7.24 (dd, 1H), 6.67 (t, 1H), 6.39 (m, 2H), 5.51-5.26 (m, 1H), 4.88 (s, 2H), 3.18-2.98 (m, 2H), 2.63-2.41 (m, 2H), 1.40 (m, 1H), 1.11 (m, 1H). MS (m/z) 781.03 [M+H]+.

Provenance & Evidence