Chloride → HCID 58920315, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)-3,3,3-trifluoropropanamide (15 mg, 0.024 mmol) in DCM (0.5 mL) was added DMSO (3.74 mg, 0.048 mmol). The reaction mixture was cooled to −78° C. and oxaly chloride (18.4 μL, 2M in DCM, 0.04 mmol) was added. After 15 min at −78° C., NEt3 (10 μL, 0.072 mmol) was added. The reaction mixture was stirred for 1 h and H2O was added to quench the reaction. The reaction mixture was concentrated and the crude mixture was purified by preparative HPLC Shimadzu-Phenomenex C18 column, 20×100 mm eluting with 30-100% MeOH (90% in H2O, 0.1% TFA) gradient over 12 min with flow rate 20 mL/min and UV detection at 220 nm. 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(1-cyano-2,2,2-trifluoroethyl)urea was isolated as a pale yellow solid (7 mg, 50% yield). LCMS: RT=3.96 min [M+H] 593.11 (LCMS Method 1); NMR: 400 MHz 1H (CDCl3) 8.27 ppm, 1H, m; 7.72 ppm, 1H, m; 7.63 ppm, 1H, d, J=12.6 Hz; 7.12 ppm, 6H, m; 6.91 ppm, 1H, m; 6.52 ppm, 2H, dd, J=20.2, 6.8 Hz; 5.81 ppm, 2H, m; 5.23 ppm, 1H, dd, J=27.3, 10.1 Hz; 4.33 ppm, 1H, dd, J=12.9, 3.3 Hz; 3.52 ppm, 1H, m.

Provenance & Evidence