89% |
With 1,1'-carbonyldiimidazole; In N,N-dimethyl-formamide; at 60℃; for 22.0h; |
Literature citation for methodology (Kimura et al., 2007). Amixture of <strong>[68302-57-8]amlexanox</strong> (1; 200 mg, 0.67 mmol), CDI (130 mg, 0.81 mmol) and DMF (5.0 mL)was stirred at room temperature for 30 min. The solution was then treated with 2-(dimethylamino)ethanol (71.7 mg, 0.81 mmol) and stirred at 60 C for 22 h. After cooling toroom temperature the mixture was added to H2O (65 mL) and stirred at room temperature for 5h. The precipitated white solid was collected, washed with H2O and dried at 60 C in vacuo toafford the free base of 6 (220 mg, 89%). 1H NMR (400 MHz, chloroform-d) delta 9.15 (s, 1H), 8.32(br s, 1H), 8.10 (d, J = 2.3 Hz, 1H), 7.58 (dd, J = 8.6, 2.3 Hz, 1H), 7.43 (d, J = 8.5 Hz, 1H), 5.88(br s, 1H), 4.46 (t, J = 5.9 Hz, 2H), 3.04 (p, J = 7.0 Hz, 1H), 2.77 (t, J = 5.9 Hz, 2H), 2.37 (s,6H), 1.31 (d, J = 6.9 Hz, 6H). MS m/z 370.2 (M+H)+. To a stirred solution of the free base (218mg, 0.59 mmol) in DCM (5 mL) was added HCl in diethyl ether (1 M; 1.77 mL). The suspensionwas stirred for 2 min and concentrated. The residue was triturated in ether, collected, and dried to give 6 hydrochloride (203 mg, 85%). 1H NMR (400 MHz, DMSO-d6) delta 10.44 (br s, 1H), 8.93 (s,1H), 8.43 (br s, 1H), 8.07 (br s, 1H), 7.92 (d, J = 2.3 Hz, 1H), 7.75 (dd, J = 8.7, 2.3 Hz, 1H), 7.55(d, J = 8.6 Hz, 1H), 4.65 (t, J = 5.0 Hz, 2H), 3.57 (m, 2H), 3.06 (p, J = 6.9 Hz, 1H), 2.87 (d, J =2.4 Hz, 6H), 1.26 (d, J = 6.9 Hz, 6H). MS m/z 370.2 (M+H)+. HPLC 97%. |