1,2-Dichloroethane → tert-butyl ((3R,4S,5S)-4-amino-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-5-methylpiperidin-3-yl)carbamate

Participants

Reaction Steps

EDC (1.5 equiv.) and HOAt (1.5 equiv.) were added to a solution of tert-butyl ((3R,4S,5S)-1-(3-aminopyridin-4-yl)-4-azido-5-methylpiperidin-3-yl)carbamate (1.0 equiv.) and 6-(2,6-difluorophenyl)-5-fluoropicolinic acid (1.3 equiv.) in DMF (0.20 M). The mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, concentrated and purified by ISCO SiO2 chromatography. To a degassed a solution of the azide (1.0 equiv.) in 2-propanol (0.10 M) was added Pd/C (0.2 equiv.). The mixture was stirred under H2 for 48 hrs. Filter the mixture over cetlite and wash the cake with MeOH. Concentrate the filtrate to yield tert-butyl ((3R,4S,5S)-4-amino-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-5-methylpiperidin-3-yl)carbamate in 58% yield). LC/MS (m/z)=557.1 (MH+), Rt=0.69 min.

Provenance & Evidence