反应详情

A solution of (+/−)-(1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate (1.0 equiv.), 1H-1,2,4-triazole (3.0 equiv.) and Cs2CO3 (3.0 equiv.) in DMF (0.15 M) was stirred at 80° C. for 5 hrs. 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 RP HPLC, followed by free basing by partitioning between an equal volume of EtOAc and Na2CO3, separating, washing with NaCl(sat), drying over MgSO4, filtering, concentrating. Purification was completed via SFC (20% MeOH, 100 mL/min, AD column) to yield tert-butyl (1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)cyclohexylcarbamate (19% yield, 99% ee) and tert-butyl (1S,2R,3R,5S)-5-(3-aminopyridin-4-yl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)cyclohexylcarbamate (19% yield, 99% ee). LC/MS (m/z)=373.3 (MH+), Rt=0.54 min.

1. customThe volatiles were removed in vacuo
2. customthe residue was partitioned between EtOAc and H2O
3. washThe organic layer was washed with Na2CO3(sat), NaCl(sat)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. custompurified by RP HPLC
8. customby partitioning between an equal volume of EtOAc and Na2CO3
9. customseparating
10. washwashing with NaCl(sat)
11. dry with materialdrying over MgSO4
12. filtrationfiltering
13. concentrationconcentrating
14. customPurification