3-Phenoxybenzoic acid → n-{2-[Methyl-(1-methyl-pyrrolidin-3-ylmethyl)-amino]-benzooxazol-5-yl}-3-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), 3-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 to yield a yellow residue. Dilute with CH2Cl2 and wash with 1.0M NaOH (2×25 mL), dry over Na2SO4, filter, and concentrate in vacuo after adsorption onto silica gel. Subject the mixture to flash column chromatography on an ISCO Companion (4 g column, 10% 2M NH3 in MeOH/CH2Cl2) to yield the desired compound as a white oil. Dilute with CH2Cl2 and n-hexane and concentrate in vacuo. Pump for 2 h to yield the desired compound as a white solid (0.027 g, 45%). mass spectrum (m/e): 457.3 (M+1), 455.3 (M−1). 1H NMR (400 MHz, CDCl3): δ 7.84 (s, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.51-7.45 (m, 2H), 7.41 (t, J=8.0 Hz, 1H), 7.37-7.29 (m, 3H), 7.20-7.10 (m, 3H), 7.04-7.00 (m, 2H), 3.59-3.48 (m, 2H), 3.18 (s, 3H), 2.74-2.50 (m, 4H), 2.38-2.33 (m, 1H), 2.35 (s, 3H), 2.05-1.95 (m, 1H), 1.59-1.49 (m, 1H).

Provenance & Evidence