Triethylamine → 4-[(2-Methoxyethoxy)methoxy]benzonitrile

Participants

Reaction Conditions

Reaction Steps

3-(3-Aminopropyl)-4-(2-methoxyethoxymethoxy)benzonitrile (88 mg, 0.33 mmol) in DMF (0.5 mL) is added to a mixture of 4-pyridin-4-yl benzoic acid (60 mg, 0.3 mmol), TBTU (106 mg, 0.33 mmol), and Et3N (0.043 mL, 0.033 mmol) in DMF (1 mL). The mixture is stirred at 35° C. for 4 hours. The solution is diluted with EtOAc (20 mL), washed with saturated NaHCO3 (3×17 mL) and brine (3×17 mL), dried over MgSO4, filtered and concentrated. The residue is chromatographed (4% MeOH/CH2Cl2) to give 3-[4-(pyridin-4-yl)-benzamido]propyl)-4-(2-methoxyethoxymethoxy)-benzonitrile (0.09 g, 0.20 mmol), contaminated with an unknown byproduct. The crude material (0.08 g, 0.18 mmol) is dissolved in CH2Cl2 (5 mL), treated with MCPBA (57-86%, 92 mg) at 0° C., a room temperature for 2 hours. The residue from aqueous workup and concentration is treated with anhydrous HCl/EtOH followed by ammonolysis as described in Example 307, part D. HPLC purification (10% MeCN/0.1% TFA in H2O to 100% MeCN) gave the title compound (0.007 g, 0.01 mmol). 1H NMR (CD3OD, 300 MHz) δ8.94 (bs, 1H), 8.65 (bs, 1H), 8.40 (m, 3H), 7.90 (m, 6H), 7.64 (d, 1H), 7.57 (dd, 1H), 6.93 (d, 1H), 3.43 (t, 2H), 2.77 (t, 2H), 1.97 (m, 2H). Ion spray MS [M+1]=391, [M+2]2+=196.

Provenance & Evidence