Reaktion #427688

Reaktionsgleichung

tert-butyl cis-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate

5-methyl-3-pyridineamine

cesium carbonate

Xantphos

→

tert-butyl cis-2-(6-(5-methylpyridin-3-ylamino)-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate

Ausbeute 87.6%

Lösungsmittel

1,4-dioxane

ethyl acetate

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled to room temperature
2. 2
   SonstigeInsoluble matter was removed by filtration
3. 3
   Waschenthe filter cake was washed with water and ethyl acetate
4. 4
   Sonstigethe organic layer was collected
5. 5
   Waschenwashed with saturated saline
6. 6
   Trocknendried over anhydrous magnesium sulfate
7. 7
   workup.DISTILLATIONthe solvent was distilled away under reduced pressure
8. 8
   SonstigeThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0 to 1:4), diisopropylether
9. 9
   workup.ADDITIONwas added
10. 10
    Filtrationsolid matter was collected by filtration

Vorschrift

5-methyl-3-pyridineamine (191 mg), cesium carbonate (1.10 g), Pd2(dba)3 (186 mg), and Xantphos (235 mg) were added to a 1,4-dioxane (14 ml) solution containing tert-butyl cis-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate (500 mg), followed by stirring at 100° C. for 2 hours in a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. Insoluble matter was removed by filtration, the filter cake was washed with water and ethyl acetate, the organic layer was collected, washed with saturated saline, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0 to 1:4), diisopropylether was added, solid matter was collected by filtration, and a light yellow solid of tert-butyl cis-2-(6-(5-methylpyridin-3-ylamino)-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate (523 mg) was thus obtained.

Quelle