Trifluoroacetic acid → HCID 178480858, compound

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of N-(4-(1-(4-methoxybenzyl)-3-(2-(4-methylpiperazin-1-yl)ethyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (4 mg, 0.006 mmol) and TFA (0.5 mL) was heated to 70° C. for 18 hours. The mixture was concentrated in vacuo, using toluene (2×5 mL) to azeotrope residual TFA. The residue was partitioned between EtOAc (5 mL) and a 1:1 water/saturated aqueous NaHCO3 (5 mL) mixture. The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×2 mL). The combined organic phases were concentrated in vacuo. The residue was loaded on to a preparative TLC plate, eluting with 10% MeOH (containing 7N NH3) in CHCl3. The product was further purified on a Waters SepPak silica gel column (2 g silica), eluting with DCM, 5% MeOH/DCM, then 5% MeOH (containing 7N NH3) in DCM to elute the product. The product was obtained as a waxy solid (1.2 mg, 34%). LCMS (ESI+): 93% purity, 220 nm, m/z 576 (M+1) detected; 1H NMR (400 MHz, MeOD-d3) δ 8.27 (d, J=6 Hz, 1H), 7.84 (m, 1H), 7.55 (m, 2H), 7.43 (m, 1H), 7.37 (t, J=9 Hz, 1H), 7.07 (t, J=9 Hz, 2H), 6.29 (d, J=6 Hz, 1H), 3.65 (m, 1H, overlaps MeOD), 3.57 (m, 1H), 2.94 (m, 2H), 2.64 (m, 8H), 2.37 (s, 3H), 1.64 (m, 4H).

Provenance & Evidence