Benzaldehyde → (+/-)-tert-butyl ((1R,2S,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-3-methyl-2-(methylamino)cyclohexyl)carbamate

HRID 879218

Reaktionsgleichung

Reaktionsgleichung von HRID 879218
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C@H:15]1[CH2:20][C@@H:19]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@@H:18]([NH2:29])[C@@H:17]([CH3:30])[CH2:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:31](=O)C1C=CC=CC=1.[B-]C#N.[Na+].C=O>CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C@H:15]1[CH2:20][C@@H:19]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@@H:18]([NH:29][CH3:31])[C@@H:17]([CH3:30])[CH2:16]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 240BenzaldehydeHCID 712FormaldehydeHCID 20587905Sodium cyanoborohydride [MI]2×HCID 86705267(+/-)-tert-butyl ((1R,2S,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-2-amino-3-methylcyclohexyl)carbamate

Produkt 1

HCID 86705268(+/-)-tert-butyl ((1R,2S,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-3-methyl-2-(methylamino)cyclohexyl)carbamateAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9942167Palladium hydroxideKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-be673beb2a204123848f535be3ac20f8
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987457B2

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