反应详情

A solution of chloride 21 (1.32 g, 6.0 mmol), Et3N (1.65 mL, 11.8 mmol) and 2-(3-methoxy-1-azetidinyl)ethylamine (277) (950 mg, 7.3 mmol) in DME (30 mL) was heated at reflux temperature for 18 h. The solution was cooled, the solvent evaporated and the residue partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (4×50 mL), the combined organic fraction dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1-oxide 34 (890 mg, 48%) as a yellow solid: mp 139-141° C.; 1H NMR δ 8.06 (s, 1H, H-9), 7.38 (s, 1H, H-5), 5.67 (br s, 1H, NH), 4.04 (p, J=5.8 Hz, 1H, CHO), 3.63-3.69 (m, 2H, CH2N), 3.47 (dt, J=5.9, 5.6 Hz, 2H, CH2N), 3.26 (s, 3H, OCH3), 2.93-3.03 (m, 6H, H-6, H-8, CH2N), 2.74 (t, J=5.9 Hz, 2H, NCH2), 2.14 (p, J=7.4 Hz, 2H, H-7); 13C NMR δ 158.7, 154.5, 148.7, 143.3, 129.8, 120.6, 114.6, 70.0, 61.4 (2), 58.0, 56.0, 39.3, 33.1, 32.3, 25.7; MS (APCI) m/z 316 (MH+, 100%). Anal. calcd for C16H21N5O2.¼H2O: C, 60.1; H, 6.8; N, 21.9. Found: C, 60.0; H, 6.6; N, 21.7%.

1. temperatureat reflux temperature for 18 h
2. temperatureThe solution was cooled
3. customthe solvent evaporated
4. customthe residue partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL)
5. extractionThe aqueous layer was extracted with DCM (4×50 mL)
6. customthe combined organic fraction dried
7. customthe solvent evaporated
8. customThe residue was purified by chromatography
9. washeluting with a gradient (0-10%) of MeOH/DCM