反应详情

温度

95 °C

To a solution of compound 8-bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 231) (150 mg) in toluene (2 mL) in a screw-capped vial under argon are added diisopropylethylamine (0.2 mL), sodium thiomethoxide (29 mg), bis(dibenzilideneacetone)palladium(0) (50 mg) and Xantphos (50 mg). The reaction mixture is heated at 95° C. for 19 hours. The mixture is then diluted with water and extracted with dichloromethane. Pooled organic extracts are dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 17% (B) to 27% (B) in 10 minutes) to afford 4-(1-methylpiperidin-4-yloxy)-8-methylsulfanyl-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene melting at 134° C.

1. extractionextracted with dichloromethane
2. dry with materialPooled organic extracts are dried over magnesium sulphate
3. filtrationfiltered
4. customthe solvent is removed under reduced pressure
5. customThe residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 17% (B) to 27% (B) in 10 minutes)