Pivalic acid → Tert-butyl 3-{1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)-pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]ethyl}pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 3-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]pyrrolidine-1-carboxylate (100 mg, 0.335 mmol), 6-bromo-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine (112 mg, 0.337 mmol), butyl di-1-adamantylphosphine (25 mg, 0.070 mmol), tris(dibenzylideneacetone)dipalladium(0) (16.3 mg, 0.018 mmol), pivalic acid (0.018 mL, 0.157 mmol), potassium carbonate (140 mg, 1.013 mmol) and N,N-dimethylacetamide (1 mL) were combined and the mixture was evacuated and purged with nitrogen 3 times then heated to 130° C. for 7 hours. The mixture was filtered then extracted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure to afford tert-butyl 3-{1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)-pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]ethyl}pyrrolidine-1-carboxylate, which was used in a subsequent step without further purification. MS ESI calc'd. for C26H30F3N5O3S [M+H]+ 550. found 550.

Provenance & Evidence