Réaction #506760

Équation de réaction

4-fluoro-2-pyridinamine

3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-benzamide

NBS

→

title compound

Rendement 55.0%

3-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide

Rendement 55.0%

Solvants

EtOAc

NaHCO3

DCM

Conditions de réaction

Traitement

1. 1
   Concentrationconcentrated under vacuum to a foam like solid
2. 2
   workup.DISSOLUTIONThe solid was dissolved in dioxane (15 mL)
3. 3
   workup.STIRRINGThe reaction was stirred under N2
4. 4
   workup.STIRRINGstirred for approximately 18 h
5. 5
   Températurecooled to rt
6. 6
   AutreThe organic layer was separated
7. 7
   Lavagewashed with brine
8. 8
   ExtractionThe combined aqueous layers were extracted with EtOAc (3×)
9. 9
   SéchageThe combined organic layers were dried over MgSO4
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated under vacuum
12. 12
    AutreThe residue was purified by silica gel chromatography

Mode opératoire

To a stirred solution of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1, step B) (0.6 g, 1.49 mmol) in DCM (15 mL) at rt under N2 was added NBS (0.278 g, 1.56 mmol). The reaction was stirred approximately 60 min, then concentrated under vacuum to a foam like solid. The solid was dissolved in dioxane (15 mL) and 4-fluoro-2-pyridinamine (0.5 g, 4.46 mmol) was added. The reaction was stirred under N2, heated to 75° C., and stirred for approximately 18 h, then cooled to rt. The reaction was diluted with EtOAc and half-saturated aqueous NaHCO3. The organic layer was separated and washed with brine. The combined aqueous layers were extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography to give the title compound of step B (0.391 g, 0.81 mmol, 55%) as a light yellow solid. MS (ESI): 480 [M+H]+.

Source