Formaldehyde → (2S)-2-(methyl(4-(5-(2'-methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)amino)butanoic acid

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Reaction Steps

Sodium cyanoborohydride (18 mg; 0.28 mmol) was added to a solution of 4-(5-(2′-methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (Example 54, step 2, 103 mg; 0.25 mmol) and (S)-2-aminobutanoic acid (52 mg; 0.50 mmol) in a mixture of methanol (3 mL), DCM (3 mL) and acetic acid (38 μl). The mixture was stirred at room temperature overnight and was filtered through a frit under positive pressure. To the filtrate was added formaldehyde (37% aqueous solution; 204 mg, 2.51 mmol) followed by addition of AcOH until the pH was in the range of 3-4 (240 mL). To the resulting mixture was added sodium cyanoborohydride (79 mg, 1.26 mmol), the mixture stirred for 16 hours, the solvent removed in vacuo and the residue purified by reverse phase HPLC to give a white solid as the title compound. 1H NMR (DMSO-d6, 400 MHz) δ 8.57-8.53 (1H, m), 8.52-8.48 (1H, m), 8.10 (2H, d, J=8.0 Hz), 7.67 (1H, d, J=7.9 Hz), 7.57 (2H, d, J=8.0 Hz), 7.40-7.35 (2H, m), 7.32-7.27 (1H, m), 7.18 (1H, d, J=7.5 Hz), 3.86 (1H, d, J=14.3 Hz), 3.72 (1H, d, J=14.3 Hz), 3.15 (1H, t, J=7.4 Hz), 2.24 (3H, s), 2.03 (3H, s), 1.76-1.60 (2H, m), 0.95 (3H, t, J=7.3 Hz). LC/MS (Method B): 510 (M+H)+. HPLC (Method D) Rt 3.39 min (Purity: 99.8%).

Provenance & Evidence