Pyridine → 4'-Fluoro-biphenyl-4-carboxylic acid {2-[methyl-(1-methyl-piperidin-4-yl)-amino]-benzooxazol-5-yl}-amide

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Reaction Steps

Add oxalyl chloride (0.16 mL, 1.82 mmol) and 3 drops of DMF to a stirring suspension of 4′-fluoro-biphenyl-4-carboxylic acid (0.197 g, 0.910 mmol) in CH2Cl2 (2.0 mL). Stir the reaction mixture at room temperature for 2 h, Concentrate the mixture in vacuo, add n-hexane, re-concentrate, and re-dissolve in CH2Cl2. Add the resultant 4′-fluoro-biphenyl-4-carbonyl chloride solution to a mixture of rac-N2-methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine (0.158 g, 0.607 mmol) and pyridine (0.05 mL) in CH2Cl2 (10 mL). Shake the reaction mixture overnight at room temperature. Wash the mixture with saturated NaHCO3 (2×20 mL), dry the organic phase over Na2SO4, filter, and concentrate the mixture in vacuo. Subject the residue to silica gel flash column chromatography (3×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as a white solid (0.106 g, 38%). mass spectrum (m/e): 459.0 (M+1), 457.0 (M−1). 1H NMR (400 MHz, CDCl3): δ 7.95-7.90 (m, 3H), 7.63 (d, J=8.0 Hz, 2H), 7.60-7.54 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.36 (dd, J=8.8, 1.6 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.18-7.11 (m, 2H), 4.21-4.11 (m, 1H), 3.07 (s, 3H), 2.97 (d, J=11.6 Hz, 2H), 2.32 (s, 3B), 2.21-2.12 (m, 2H), 2.00-1.88 (m, 2H), 1.83-1.75 (m, 2H).

Provenance & Evidence