反应详情

To a solution of (1R,2R,4R,6S)-4-(3-aminopyridin-4-yl)-2-(tert-butoxycarbonylamino)-6-methylcyclohexyl acetate (1.0 equiv.) in DMF/Ethanol (1/5, 0.05 M) was added 6-(2,6-difluorophenyl)-5-fluoropicolinic acid (1.3 equiv.), aza-HOBt (1.3 equiv.) and EDC (1.3 equiv.). The mixture was stirred at rt for 6 hrs. The solution was diluted with EtOAc, washed with H2O, 1N NaOH, NaCl (sat.), dried over MgSO4, filtered and concentrated to yield crude protected amide. The material was dissolved in EtOH (0.45 M), Cs2CO3 (1.0 equiv.) was added and the solution was submerged in a 60° C. oil bath and stirred for 90 mins. The volatiles were removed in vacuo; the residue was partitioned between with EtOAc and H2O. The organic layer was washed with NaCl(sat), dried over MgSO4, filtered, concentrated and pumped on to yield tert-butyl (1R,2R,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-hydroxy-3-methylcyclohexylcarbamate in 99% yield. LC/MS (m/z)=557.3 (MH+), Rt=0.80 min.

1. washwashed with H2O, 1N NaOH, NaCl (sat.)
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. customto yield crude protected amide
6. customwas submerged in a 60° C.
7. stirringstirred for 90 mins
8. customThe volatiles were removed in vacuo
9. customthe residue was partitioned between with EtOAc and H2O
10. washThe organic layer was washed with NaCl(sat)
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated