反应详情

温度

55 °C

N-Benzoyl-N-[2-(1-methyl-4-phenyl-1H-imidazol-5-yl)[1,3]thiazolo[5,4-d]pyrimidin-7-yl]benzamide (Intermediate 96) (0.05 g) was dissolved/suspended in MeCN (5 mL), dimethylcarbamyl chloride (0.015 mL) added, then benzaldehyde (16 mg) and DIPEA (0.05 mL). The reaction mixture was heated at reflux for 24 hours then additional dimethylcarbamyl chloride (0.015 mL), benzaldehyde (16 mg) and DIPEA (0.05 mL) added. After heating for 5 days, the reaction mixture was concentrated in vacuo, diluted with saturated NaHCO3 solution (5 mL) then extracted with DCM (2×10 mL). The combined organics were dried (MgSO4), filtered and concentrated in vacuo to give a brown residue which was dissolved in MeOH (2 mL)/concentrated aqueous NH3 (2 mL). The reaction mixture was heated at 55° C. for 1 hours then concentrated in vacuo, diluted with 2M NaOH (8 mL) and extracted with DCM (1×20 mL). The organic layer was dried (MgSO4), filtered, concentrated in vacuo giving a residue which was purified by flash chromatography on silica (2% MeOH/DCM) to give the title compound as a colourless solid (0.033 g, 68%);

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 24 hours
3. temperatureAfter heating for 5 days
4. concentrationthe reaction mixture was concentrated in vacuo
5. additiondiluted with saturated NaHCO3 solution (5 mL)
6. extractionthen extracted with DCM (2×10 mL)
7. dry with materialThe combined organics were dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give a brown residue which
11. concentrationthen concentrated in vacuo
12. additiondiluted with 2M NaOH (8 mL)
13. extractionextracted with DCM (1×20 mL)
14. dry with materialThe organic layer was dried (MgSO4)
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customgiving a residue which
18. customwas purified by flash chromatography on silica (2% MeOH/DCM)