反应详情

温度

100 °C

A solution of tert-butyl 3-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate (413 mg) in dioxane (3 ml) was added to a flask charged with 3-amino-6-chloro-4-(methylamino)picolinonitrile (160 mg), tris(dibenzylideneacetone)dipalladium (0) (40.1 mg), tricyclohexylphosphine (29.5 mg) and potassium phosphate (372 mg). Water (1.2 ml) was added and the reaction was placed under a nitrogen atmosphere and heated to 100° C. for 2 hours. The mixture was allowed to cool to room temperature then diluted with EtOAc (150 ml) filtered through celite and washed with water (2×100 ml) and brine (50 ml). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure to afford crude product as a brown oil. Purification by flash chromatography (50 g silica column, DCM to 5% MeOH in DCM mobile phase) afforded product still containing minor impurities. DCM was added to the residue causing solid to crash out of solution. The solid was collected by filtration and washed with ether to yield desired product tert-butyl 3-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate.

1. temperatureto cool to room temperature
2. filtrationfiltered through celite
3. washwashed with water (2×100 ml) and brine (50 ml)
4. dry with materialOrganics were dried over sodium sulphate and solvent
5. customevaporated under reduced pressure
6. customto afford crude product as a brown oil
7. customPurification by flash chromatography (50 g silica column, DCM to 5% MeOH in DCM mobile phase)
8. customafforded product
9. additionstill containing minor impurities
10. filtrationThe solid was collected by filtration
11. washwashed with ether