Trifluoroacetic acid → N-[3-[5-amino-6-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-yl]prop-2-ynyl]methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 2-[6-(3-aminoprop-1-ynyl)-3-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl]-6-methyl-benzimidazole-1-carboxylate (90 mg, 0.1555 mmol) and Et3N (23.60 mg, 32.51 μL, 0.2332 mmol) were dissolved in DCM (10 mL) and cooled to 0° C. in and ice bath. Mesyl chloride (21.38 mg, 14.45 μL, 0.1866 mmol) as a solution in DCM (1 mL) was added dropwise and the reaction stirred at 0° C. for 20 minutes. The reaction mixture was washed with saturated aqueous NaHCO3 (×1) and brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was redissolved in DCM (10 mL) and TFA (177.3 mg, 119.8 μL, 1.555 mmol) added. The reaction mixture was stirred at ambient temperature for 1 hour then concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 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 title compound as an yellow solid (2 mg, 4% Yield). 1H NMR (400.0 MHz, D4-MeOH) δ 1.6 (3H, s), 2.25 (3H, s), 3.25 (2H, s), 6.25 (1H, d), 6.55 (1H, s), 6.7 (1H, d), 7.3 (1H, s); MS (ES+) 357.

Provenance & Evidence