Acetic Acid → HCID 67496521, compound

Participants

Reaction Steps

To a solution of tert-butyl (S)-1-(3-(2-aminopyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (36.C) (200 mg, 0.46 mmol) in THF (2 mL) was added 4M HCl in dioxane (2 mL, 8 mmol). The mixture was stirred at room temperature for 2 hours and then was concentrated. The residue was neutralized with saturated aqueous NaHCO3 and extracted with 4:1 DCM/isopropanol. The organic layers were combined, washed with brine, dried on MgSO4 and concentrated. The residue was dissolved in DCM and then thiazole-4-carbaldehyde (56 mg, 0.50 mmol) was added. The mixture was stirred for 1 h at room temperature at which time acetic acid (28 μL, 0.46 mmol) and sodium triacetoxyborohydride (293 mg, 1.38 mmol) were added. The mixture was stirred at room temperature for additional 2 hours, concentrated and the residue purified by reverse phase preparative HPLC to afford (2S)—N-(3-(2-aminopyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide 36 (58 mg, 29% yield) as a white solid. LCMS ESI (pos.) m/e: 430.1 (M+1): 1H NMR (400 MHz, MeOH-D4) δ ppm 9.12 (d, J=1.96 Hz, 1H), 7.91-7.97 (m, 2H), 7.79 (d, J=1.96 Hz, 1H), 7.42-7.57 (m, 3H), 7.25-7.36 (m, 5H), 7.18-7.21 (m, 1H), 7.13-7.17 (m, 1H), 4.42-4.54 (m, 2H), 4.25 (dd, J=9.39, 5.87 Hz, 1H), 3.42 (dd, J=13.30, 5.87 Hz, 1H), 3.25 (dd, J=13.30, 9.00 Hz, 1H).

Provenance & Evidence