反应详情

6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 2, 600 mg, 2.186 mmol), (R)-tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate (549 mg, 2.404 mmol) and DIPEA (0.764 mL, 4.37 mmol) in DMA (3.0 mL) was heated at 90° C. for 3 h. The mixture was cooled and added to crushed ice, stirred for 30 min, then extracted with EtOAc (100 mL×3). The combined organic extracts were washed with brine, filtered and concentrated to afford brown oil, which was added to water and stirred for 2 h to afford a solid which was collected by vacuum filtration and dried to afford the title compound as a tan solid (546 mg, 1.17 mmol, 54%). HPLC (Method B) retention time=3.91 min. LCMS (m+1)=466/468(1:1).

1. temperatureThe mixture was cooled
2. additionadded
3. customto crushed ice
4. extractionextracted with EtOAc (100 mL×3)
5. washThe combined organic extracts were washed with brine
6. filtrationfiltered
7. concentrationconcentrated
8. customto afford brown oil, which
9. stirringstirred for 2 h
10. customto afford a solid which
11. filtrationwas collected by vacuum filtration
12. customdried