Trifluoroacetic acid → HCID 54670944, compound

Participants

Reaction Steps

TFA (1 mL) was added to a stirred solution of tert-Butyl (3-(3-((3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)ethynyl)phenoxy)propyl)carbamate (crude residue used directly from Step 1) in DCM (5 mL) at ambient temperature. The reaction was allowed to stir at this temperature for 6 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The reaction mixture was passed through a 5 g SCX-2 cartridge and washed with MeOH. The product was eluted by washing the cartridge with 2M NH3 in MeOH. The solvent was removed in vacuo and the residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the mono-TFA salt of the title compound as a yellow solid (24 mg, 37% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, 6H), 2.00-2.06 (m, 2H), 2.97-3.02 (m, 2H), 3.46 (sept, 1H), 4.13 (t, 2H), 7.05-7.08 (m, 1H), 7.17 (s, 2H), 7.39-7.41 (m, 3H), 7.71 (s, 3H), 7.91 (d, 2H), 8.23 (d, 2H) and 8.77 (s, 1H) ppm; MS (ES+) 451.2.

Provenance & Evidence