反应详情

温度

50 °C

To a stirred orange mixture of tert-butyl 5-(quinazolin-7-yl)thiazol-2-ylcarbamate (22 mg, 67 μmol) and Cs2CO3 (44 mg, 134 μmol) in DMF (1.0 mL), was slowly added a solution of the cyclic sulfamidate (38 mg, 100 μmol) in DMF (0.5 mL) at 50° C. The resulting light yellow mixture was stirred at 50° C. for 30 minutes. The mixture was then cooled to 0° C. and was then diluted with EtOAc and 1N HCl(aq) and the entire mixture was stirred at room temperature for 30 minutes. The layers were separated, the aqueous layer was extracted with EtOAc (5 mL×3), and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the crude residue, which was taken up in a solution of DCM (1.5 mL), and TFA (1.5 mL) was slowly added. The overall solution was stirred at room temperature for 30 minutes and concentrated. The crude residue was dissolved in DCM and mixed with silica. The solvent was evaporated, and the residue was purified with flash column chromatography (pure DCM→10% MeOH in DCM) to obtain N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(quinazolin-7-yl)thiazol-2-amine (12 mg, 42%) as a yellow solid.

1. temperatureThe mixture was then cooled to 0° C.
2. stirringthe entire mixture was stirred at room temperature for 30 minutes
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with EtOAc (5 mL×3)
5. washthe combined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customto give the crude residue, which
9. additionwas slowly added
10. stirringThe overall solution was stirred at room temperature for 30 minutes
11. concentrationconcentrated
12. dissolutionThe crude residue was dissolved in DCM
13. additionmixed with silica
14. customThe solvent was evaporated
15. customthe residue was purified with flash column chromatography (pure DCM→10% MeOH in DCM)