反应详情

To intermediate 38 (0.35 g, 0.86 mmol) in dry DMF (25 mL) was added 3-((4-fluorophenyl)(methyl)amino)-3-oxopropanoic acid (44) [US 2007/0004675 A1] (0.36 g, 1.7 mmol) [Met-036], and EDC.HCl (0.33 g, 1.7 mmol) and the mixture was stirred at r.t. for 2 h. The mixture was then partitioned between ethyl acetate and water; the organic phase was collected, washed with water, saturated NaHCO3, and brine, dried (anhydrous MgSO4), filtered and concentrated. The crude product was dissolved in acetone (50 mL) to give a colorless solution. The solution was diluted with water (20 mL) and TFA (2 mL), and heated to reflux for 3 h. It was then cooled and concentrated. The residue was then partitioned between ethyl acetate and water, the organic phase was collected, washed with water, saturated NaHCO3, and brine, dried (anhydrous MgSO4), filtered and concentrated to produce intermediate 45 (0.27 g, 57% yield). MS (m/z): 559.2 (M+H).

1. customThe mixture was then partitioned between ethyl acetate and water
2. customthe organic phase was collected
3. washwashed with water, saturated NaHCO3, and brine
4. dry with materialdried (anhydrous MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe crude product was dissolved in acetone (50 mL)
8. customto give a colorless solution
9. temperatureheated
10. temperatureto reflux for 3 h
11. temperatureIt was then cooled
12. concentrationconcentrated
13. customThe residue was then partitioned between ethyl acetate and water
14. customthe organic phase was collected
15. washwashed with water, saturated NaHCO3, and brine
16. dry with materialdried (anhydrous MgSO4)
17. filtrationfiltered
18. concentrationconcentrated