Trifluoroacetic acid → HCID 54671132, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (151.3 mg, 208.4 μL, 1.495 mmol) was added to a stirred solution of tert-butyl N-[5-(4-(isopropylsulfonyl)phenyl)-3-ethynylpyrazin-2-yl]-N-tertbutoxycarbonyl-carbamate (75 mg, 0.1495 mmol), 3-bromobenzamide (44.85 mg, 0.2242 mmol), copper (I) iodide (3.417 mg, 0.01794 mmol) and PdCl2(PPh3)2 (5.247 mg, 0.007475 mmol) in DMF (1.5 mL) and the reaction was stirred at 120° C. for 5 minutes under fixed power (300 W) microwave conditions. The reaction mixture was cooled to ambient temperature and diluted with EtOAc and 1MHCl/brine (1:1). The layers were separated and the aqueous layer was extracted with ethyl acetate (×2). The combined organics extracts washed with brine (×2), dried over (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (5 mL) and TFA (1 mL, 12.98 mmol) was added. The reaction was stirred at ambient temperature for 40 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The material 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, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a beige solid (11 mg, 17% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, 6H), 3.45 (sept, 1H), 7.22 (br s, 2H), 7.53 (br s, 1H), 7.57 (t, 1H), 7.91 (d, 2H), 7.94 (d, 2H), 8.10 (s, 1H), 8.24 (d, 2H), 8.29 (d, 1H) and 8.78 (s, 1H) ppm; MS (ES+) 421.1.

Provenance & Evidence