Acetic Acid → HCID 67497711, compound

Participants

Reaction Steps

To a solution of (S)-tert-butyl 2-(3-(2-amino-3-phenylpropanamido)-5-(pyridin-4-yl)phenyl)-2,2-difluoroacetate 52.F (300 mg, 0.64 mmol) in DCM (5 mL) was added thiazole-4-carbaldehyde (73 mg, 0.64 mmol). The mixture was stirred for 1 h at room temperature, then acetic acid (30 μL, 0.64 mmol) and sodium triacetoxyborohydride (408 mg, 1.93 mmol) were added and the mixture stirred at room temperature for an additional 2 hours. The mixture was then concentrated and the residue was stirred in THF (5 mL) and concentrated HCl (5 mL) at 50° C. overnight. The mixture was then concentrated and the crude product purified by reverse phase chromatography (0-100% CH3CN/water+0.5% TFA) to afford (S)-2,2-difluoro-2-(3-(3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)phenyl)acetic acid 52 as a white solid (140 mg, 43% yield). LCMS ESI (pos.) m/e: 509.0. (M+1). 1H NMR (500 MHz, MeOH-D4) δ ppm 9.14 (d, J=1.96 Hz, 1H), 8.81-8.87 (m, 2H), 8.16 (t, J=1.83 Hz, 1H), 8.12-8.15 (m, 2H), 7.88 (s, 1H), 7.81 (d, J=1.96 Hz, 1H), 7.72 (s, 1H), 7.24-7.37 (m, 5H), 4.46-4.59 (m, 2H), 4.27 (dd, J=9.29, 5.87 Hz, 1H), 3.40-3.51 (m, 1H), 3.27 (dd, J=13.45, 9.29 Hz, 1H).

Provenance & Evidence