反应详情

To a solution of (+/−)-tert-butyl ((1R,2S,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-2-amino-3-methylcyclohexyl)carbamate (1.0 equiv.) in MeOH (0.10 M) was added benzaldehyde (1.3 equiv.). After 3 hrs, sodium cyanotrihydroborate (2.5 equiv.) was added and the mixture was stirred at rt for 16 hrs. The reaction mixture was quenched by the addition of water, and volatiles were removed in vacuo. The mixture was extracted with ethyl acetate. The combined organic phases were dried with sodium sulfate, filtered and concentrated. The residue was dissolved in MeOH (0.10 M) and paraformaldehyde (5.0 equiv.) was added. After 16 hrs, sodium cyanotrihydroborate (5.0 equiv.) was added and the mixture was left stirred at rt for 16 hrs. The reaction was quenched by the addition of water, and volatiles were removed in vacuo. The mixture was extracted with DCM. The combined organic phases were dried with sodium sulfate, filtered, concentrated and purified by ISCO Chromatography. The product was dissolved in MeOH (0.10 M) and treated with Pd(OH)2 (0.50 equiv.) under H2 for 5 hrs at RT. The reaction was filtered through a pad of celite and the cake was washed with MeOH. The organics were concentrated to yield (+/−)-tert-butyl ((1R,2S,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-3-methyl-2-(methylamino)cyclohexyl)carbamate in 75% yield. LC/MS (m/z)=435.2 (MH+), Rt=0.64 min.

1. customThe reaction mixture was quenched by the addition of water, and volatiles
2. customwere removed in vacuo
3. extractionThe mixture was extracted with ethyl acetate
4. dry with materialThe combined organic phases were dried with sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in MeOH (0.10 M)
8. waitAfter 16 hrs
9. waitthe mixture was left
10. stirringstirred at rt for 16 hrs
11. customThe reaction was quenched by the addition of water, and volatiles
12. customwere removed in vacuo
13. extractionThe mixture was extracted with DCM
14. dry with materialThe combined organic phases were dried with sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. custompurified by ISCO Chromatography
18. dissolutionThe product was dissolved in MeOH (0.10 M)
19. filtrationThe reaction was filtered through a pad of celite
20. washthe cake was washed with MeOH
21. concentrationThe organics were concentrated