反应详情

温度

100 °C

A suspension of tert-butyl 4-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-yloxy)ethyl)piperidine-1-carboxylate (8.95 g), 3-amino-6-chloro-4-(methylamino)picolinonitrile (2.29 g), tris(dibenzylideneacetone)dipalladium (0) (0.59 g), tricyclohexylphosphine (0.43 g) and potassium phosphate (5.48 g) in 1,4-dioxane (80 ml) and water (40 ml) was stirred at 100° C. under nitrogen for 2 h. The reaction mixture was cooled and partitioned between water and ethyl acetate, washed with water, brine, dried over sodium sulphate, filtered and concentrated. Purified by Biotage SNAP cartridge KP-Sil column (340 g, heptane:ethyl acetate=1:0, 2:1, 1:1 to 1:2) to give 6.43 g light brown solid as tert-butyl 4-(2-(5-amino-6-cyano-4-(methylamino)-5′-(trifluoromethyl)-2,3′-bipyridin-6′-yloxy)ethyl)piperidine-1-carboxylate (99%, 90% purity).

1. temperatureThe reaction mixture was cooled
2. custompartitioned between water and ethyl acetate
3. washwashed with water, brine
4. dry with materialdried over sodium sulphate
5. filtrationfiltered
6. concentrationconcentrated
7. customPurified by Biotage SNAP cartridge KP-Sil column (340 g, heptane:ethyl acetate=1:0, 2:1, 1:1 to 1:2)