反应详情

To a solution of (+/−)-tert-butyl ((1R,2S,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-3-methyl-2-(methylamino)cyclohexyl)carbamate (1.0 equiv.) in DCM (0.05 M) at 0° C. was added DIEA (3.0 equiv.) and then methyl chloroformate (1.5 equiv.). The homogeneous solution was left standing at 0° C. at for 4 hrs. The reaction was quenched partitioned between NaHCO3 solution and EtOAc. The organic layer was washed with Brine, dried over Na2SO4, concentrated and purified by ISCO chromatography. The product was treated with 4 M HCl in dioxane (30.0 equiv.) at rt for 1 hour. The volatiles were removed in vacuo and the solid was pumped on for 5 minutes on the high vac. To the residue was added CH2Cl2 (0.15 M), DIEA (5.0 equiv.) and tert-butyl 2,5-dioxopyrrolidin-1-yl carbonate (1.6 equiv.). The solution was left stirring at rt for 1 hr. The volatiles were removed in vacuo and the residue was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat.), NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield (+/−)-methyl ((1S,2R,4R,6S)-4-(3-aminopyridin-4-yl)-2-((tert-butoxycarbonyl)amino)-6-methylcyclohexyl)(methyl)carbamate in 20% yield. LC/MS (m/z)=393.2 (MH+), Rt=0.60 min.

1. waitThe homogeneous solution was left
2. customstanding at 0° C. at for 4 hrs
3. customThe reaction was quenched
4. custompartitioned between NaHCO3 solution and EtOAc
5. washThe organic layer was washed with Brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. custompurified by ISCO chromatography
9. customThe volatiles were removed in vacuo
10. customwas pumped on for 5 minutes on the high vac
11. waitThe solution was left
12. customThe volatiles were removed in vacuo
13. customthe residue was partitioned between EtOAc and H2O
14. washThe organic layer was washed with Na2CO3(sat.), NaCl(sat.)
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated
18. custompurified by ISCO SiO2 chromatography