1,2-Dichloroethane → tert-butyl (1R,2S,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-hydroxy-3-methylcyclohexylcarbamate

HRID 705254

Reaktionsgleichung

Reaktionsgleichung von HRID 705254
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C@H:8]1[CH2:24][C@H:12]2[N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])C(=O)[O:15][C@H:11]2[C@@H:10]([CH3:25])[CH2:9]1.[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[C:34]1[N:39]=[C:38]([C:40](O)=[O:41])[CH:37]=[CH:36][C:35]=1[F:43].C(Cl)CCl.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.CCO>[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[C:34]1[N:39]=[C:38]([C:40]([NH:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[C@H:8]2[CH2:24][C@@H:12]([NH:13][C:17](=[O:18])[O:19][C:20]([CH3:22])([CH3:23])[CH3:21])[C@@H:11]([OH:15])[C@@H:10]([CH3:25])[CH2:9]2)=[O:41])[CH:37]=[CH:36][C:35]=1[F:43]

Komponenten

8

Edukt 4

HCID 111,2-DichloroethaneHCID 10796Cesium carbonateHCID 592265526-(2,6-Difluorophenyl)-5-fluoropicolinic acidHCID 90055847(3aR,5R,7S,7aS)-tert-butyl 5-(3-aminopyridin-4-yl)-7-methyl-2-oxohexahydrobenzo[d]oxazole-3(2H)-carboxylate

Produkt 1

HCID 86705216tert-butyl (1R,2S,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-hydroxy-3-methylcyclohexylcarbamateAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of (3aR,5R,7S,7aS)-tert-butyl 5-(3-aminopyridin-4-yl)-7-methyl-2-oxohexahydrobenzo[d]oxazole-3(2H)-carboxylate (1.0 equiv.) in DMF (0.2 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 16 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,2S,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-hydroxy-3-methylcyclohexylcarbamate in 100% yield. LC/MS (m/z)=557.3 (MH+), Rt=0.83 min.

Aufarbeitung

  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 The volatiles
  8. customwere 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

Quellen und Nachweise

ORD-Eintrag
ord-1003449b27584f698c3f27d2a77be4a6
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09173883B2

Verknüpfte Notizen

Wird geladen…