反应详情

Dissolve 5-(3-amino-4-fluorophenylethynyl)-nicotinonitrile, (prepared as described in EXAMPLE 160), (0.4 g, 1.7 mmol) in anhydrous pyridine. Add a solution of methylcarbamyl chloride (0.17 g, 1.8 mmol) in anhydrous tetrahydrofuran carefully to the reaction and stir overnight at room temperature. Concentrate and dissolve the crude reaction in ethyl acetate and water. Wash the organic layer with water, an aqueous saturated solution of sodium chloride, dry (potassium carbonate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 10:90 ethyl acetate:dichloromethane, and then further purify on C-18 silica, eluting with 10:90 to 50:50 using an aqueous 0.1% solution of trifluoroacetic acid and a 0.1% solution of trifluoroacetic acid in acetonitrile). Concentrate, partition the residue between ethyl acetate and an aqueous saturated solution of sodium bicarbonate and separate the layers. Wash the organic layer with an aqueous saturated solution of sodium chloride, dry (potassium carbonate), filter and concentrate to give the title compound as a white solid (25 mg, 5%).

1. customcarefully to the reaction
2. concentrationConcentrate
3. dissolutiondissolve the crude
4. customreaction in ethyl acetate
5. washWash the organic layer with water
6. dry with materialan aqueous saturated solution of sodium chloride, dry (potassium carbonate)
7. filtrationfilter
8. concentrationconcentrate
9. custompurify (silica gel chromatography
10. washeluting with 0:100 to 10:90 ethyl acetate
11. customdichloromethane, and then further purify on C-18 silica
12. washeluting with 10:90 to 50:50 using an aqueous 0.1% solution of trifluoroacetic acid
13. concentrationConcentrate
14. custompartition the residue between ethyl acetate
15. customan aqueous saturated solution of sodium bicarbonate and separate the layers
16. washWash the organic layer with an aqueous saturated solution of sodium chloride
17. dry with materialdry (potassium carbonate)
18. filtrationfilter
19. concentrationconcentrate