反应详情

温度

130 °C

Dissolve 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (1.7 g, 5.66 mmol) and (S)-2-(2-methoxy-ethyl)-piperazine (2.45 g, 17.0 mmol) in dimethylsulfoxide/toluene (1:2)(21 ml), stir under nitrogen and heat in an oil bath at 130° C. for 43 hours. Cool to ambient temperature. Dilute the mixture with one volume water and two volumes ethyl acetate, separate layers and extract the aqueous layer with ethyl acetate. Basify the aqueous layer with ammonium hydroxide and extract with ethyl acetate. Combine all ethyl acetate extracts and wash with water and brine. Dry the organic phase (Na2SO4), filter and concentrate under reduced pressure. Purify by silica gel chromatography (eluent: 0-10% 2N ammonia in methanol/dichloromethane) to give the title compound (840 mg, 38%): Mass Spectrum (ESMS) 393 (M+1); 391 (M−1).

1. temperatureCool to ambient temperature
2. customseparate layers
3. extractionextract the aqueous layer with ethyl acetate
4. extractionextract with ethyl acetate
5. washwash with water and brine
6. dry with materialDry the organic phase (Na2SO4)
7. filtrationfilter
8. concentrationconcentrate under reduced pressure
9. customPurify by silica gel chromatography (eluent: 0-10% 2N ammonia in methanol/dichloromethane)