反应详情

To solution of 6-bromo-4-((3S,4S)-4-methylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydrogen iodide salt prepared as previously described in Step 1 of Example 158 (200 mg, 0.429 mmol), 2-cyanoacetic acid (43.8 mg, 0.515 mmol) and BOP (285 mg, 0.644 mmol) in DMF (2 mL) was added DIPEA (0.225 mL, 1.288 mmol) and the resulting mixture was stirred at rt for 4 h. The reaction mixture was added to water (˜5 volumes) and the pH was adjusted to ˜7 with 1 N HCl and the resulting cloudy mixture was extracted with EtOAc (150 mL×2). The combined organic extracts were washed with water, brine, dried over anhyd. magnesium sulfate, filtered and concentrated to afford the title compound which was used directly in the next transformation. HPLC (method B) retention time=2.55 min. LCMS (m+1)=405.

1. extractionthe resulting cloudy mixture was extracted with EtOAc (150 mL×2)
2. washThe combined organic extracts were washed with water, brine
3. customdried over anhyd
4. filtrationmagnesium sulfate, filtered
5. concentrationconcentrated