反应详情

温度

120 °C

To a solution of 2-[bis-(2-chloroethyl)amino]-4-chloro-6-methyl10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid [prepared by hydrolysis of compound of Example 12, 0.5 g, 1.044 mmol], in methanol (8 mL), aminoethanol (0.25 mL, 4.17 mmol) was added and heated to 120° C. in a sealed reactor for 4 h. The reaction mixture was cooled and the solvent was removed under reduced pressure. To the residue, methanolic HCl (20 mL) was added and refluxed for 3 h. Solvent was removed and the reaction mixture was basified to pH 8 using sodium carbonate solution and extracted using ethyl acetate (3×25 mL). The organic layer was washed with water and brine solution, concentrated and the crude product was purified by column chromatography (silica gel, 1% methanol in chloroform) to obtain the title compound. Yield: 0.317 g, (67.13%); 1H NMR (DMSO-d6, 300 MHz): δ 2.4 (t, 2H, CH2), 2.48 (s, 4H, 2CH2), 2.63 (s, 3H, CH3), 3.17 (s, 4H, 2CH2), 3.41 (t, 2H, CH2), 3.86 (s, 3H, OCH3), 4.44 (t, 1H, OH), 5.15 (s, 2H, CH2), 7.04 (s, 1H, Ar), 7.12 (s, 1H, Ar), 8.08 (s, 1H, Ar), 8.15 (s, 1H, Ar); MS: m/e (ES+) 481 (M+1); analysis: C22H25ClN2O6S requires C, 54.94; H, 5.24; N, 5.82; Cl, 7.37; S, 6.67. found: C, 54.78; H, 5.34; N, 5.7; Cl, 7.87; S, 6.88%.

1. temperatureThe reaction mixture was cooled
2. customthe solvent was removed under reduced pressure
3. additionTo the residue, methanolic HCl (20 mL) was added
4. temperaturerefluxed for 3 h
5. customSolvent was removed
6. extractionextracted
7. washThe organic layer was washed with water and brine solution
8. concentrationconcentrated
9. customthe crude product was purified by column chromatography (silica gel, 1% methanol in chloroform)