Diisopropylethylamine → (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

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Reaction Steps

A flask was charged with (2S,4R)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.88 g, 2.69 mmol), prepared as in Reference 8, 2-(1H-1,2,4-triazol-1-yl)acetic acid (340 mg, 2.69 mmol), DIEA (3.0 mL, 17 mmol), HATU (1.12 g, 2.96 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3) to give (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.72 g, 1.66 mmol, 62% yield) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): 10.20 (s, 1H), 8.46 (s, 1H), 7.97 (s, 1H), 7.57 (d, J=8.8 Hz, 2H), 7.22-7.17 (m, 2H), 7.03-6.95 (m, 4H), 5.38-5.26 (m, 2H), 4.59-4.55 (m, 1H), 4.08-3.94 (m, 2H), 3.84-3.50 (m, 2H), 2.39-2.32 (m, 1H). MS (EI) for C22H19FN6O3. found 517.3 (MH+).

Provenance & Evidence