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

반응식

HRID 705254 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 702Ethanol용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1003449b27584f698c3f27d2a77be4a6
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09173883B2

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