Acetic Acid → (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-(benzylamino)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

Participants

Reaction Steps

A flask was charged with (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (150 mg, 0.302 mmol), benzaldehyde (0.031 mL, 0.30 mmol), methylene chloride (5 mL), acetic acid (0.140 mL, 2.45 mmol) and sodium triacetoxyborohydride (22 mg, 0.45 mmol). The reaction mixture was stirred at ambient temperature for 16 hours and then diluted with 2N sodium hydroxide (10 mL). The dilution was extracted with ethyl acetate (20 mL) and the extract was washed with brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give Compound 173, (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-(benzylamino)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (47 mg, 0.091 mmol, 30%), as an off-white solid. 1H-NMR (400 MHz, DMSO-D6): 11.94 (s, 1H), 10.09 (s, 1H), 7.60 (d, 2H), 7.34-7.28 (m, 4H), 7.25-7.17 (m, 3H), 7.03-6.96 (m, 6H), 4.48 (t, 1H), 3.60-3.32 (m, 7H), 2.12-1.99 (m, 2H). MS (EI) for C29H28FN5O3. found 513.9 (MH+).

Provenance & Evidence