4-Phenoxybenzoic acid → n-{2-[Methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-4-phenoxy-benzamide

Participants

Reaction Steps

Combine rac-N2-methyl-N2-(1-methyl-pyrrolidin-3-ylmethyl)-benzooxazole-2,5-diamine (0.034 g, 0.131 mmol), 4-phenoxy-benzoic acid (0.042 g, 0.196 mmol), HATU (0.050 g, 0.131 mmol), polystyrene-bound diisopropylamine (0.327 g, loading: 2.0 to 3.5 mmol/g), and CH2Cl2 (10 mL). Shake the mixture overnight at room temperature. Filter the mixture and wash the polystyrene resin with 1:1 CH2Cl2/MeOH. Concentrate the solution in vacuo. Dilute with CH2Cl2, wash with 1.0M NaOH (2×25 mL), dry over Na2SO4, filter, and concentrate in vacuo. Subject the residue to silica gel flash column chromatography on an ISCO Companion (4 g column, eluting with 10% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as a white oil. Dissolve in CH2Cl2 and add n-hexane. Re-concentrate to yield the desired product as a white solid (0.031 g, 52%). mass spectrum (m/e): 457.3 (M+1), 455.3 (M−1). 1H NMR (400 MHz, DMSO-d6): δ 10.12 (s, 1H), 8.01-7.99 (m, 2H), 7.70-7.68 (m, 1H), 7.49-7.42 (m, 2H), 7.35-7.32 (m, 2H), 7.25-7.20 (m, 1H), 7.13-7.07 (m, 4H), 3.52-3.47 (d, J=8.0 Hz, 2H), 3.12 (s, 3H), 2.66-2.55 (m, 1H), 2.55-2.47 (m, 2H), 2.43-2.35 (m, 1H), 2.55-2.47 (m, 2H), 2.43-2.35 (m, 1H), 2.28-2.24 (m, 1H), 2.23 (s, 3H), 1.93-1.83 (m, 1H), 1.49-1.39 (m, 1H).

Provenance & Evidence