Lithium Hydroxide → N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,6-difluorobenzamide

HRID 1160005

Reaktionsgleichung

Reaktionsgleichung von HRID 1160005
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:30][CH3:31])=[C:21]([NH:23][C:24](=[O:29])C(F)(F)F)[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[Li+].[OH-].[F:34][C:35]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:36]=1C(Cl)=O.C(O)C(N)(CO)CO>CN(C=O)C.O.C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:30][CH3:31])=[C:21]([NH:23][C:24](=[O:29])[C:36]4[C:35]([F:34])=[CH:43][CH:42]=[CH:41][C:40]=4[F:44])[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1

Komponenten

8

Edukt 4

HCID 3939Lithium HydroxideHCID 6503Tris(hydroxymethyl)aminomethaneHCID 874382,6-Difluorobenzoyl chlorideHCID 59511425N-[5-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide

Produkt 1

HCID 59513745N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,6-difluorobenzamideAusbeute 100,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide (370 mg, 0.83 mmol) and 1M LiOH (4.97 ml, 4.97 mmol) in 10:1 THF:H2O (10 mL) was heated at 50° C. overnight. The reaction was washed with brine (25 mL), aqueous layer extracted with EtOAc (25 mL), organic layers combined, filtered through a cotton plug, and solvent removed by rotary evaporation. After high vacuum removal of residual solvent, the crude mixture was dissolved in THF (25 mL) and to this was added 2,6-difluorobenzoyl chloride (920 mg, 5.25 mmol). After stirring 3 h at rt, DMF (25 mL) was added to dissolve any suspended solids followed by the addition of excess polymer-bound trisamine resin. Upon overnight stirring, the amine resin was removed by vacuum filtration, rinsed with MeOH (50 mL), and filtrate concentrated under reduced pressure to afford the desired amide (410 mg, 79%) as an off-white solid. ESIMS (M+H)+=492.

Aufarbeitung

  1. washThe reaction was washed with brine (25 mL), aqueous layer
  2. extractionextracted with EtOAc (25 mL), organic layers
  3. filtrationfiltered through a cotton plug, and solvent
  4. customremoved by rotary evaporation
  5. customAfter high vacuum removal of residual solvent
  6. dissolutionthe crude mixture was dissolved in THF (25 mL)
  7. dissolutionto dissolve any suspended solids
  8. stirringUpon overnight stirring
  9. customthe amine resin was removed by vacuum filtration
  10. washrinsed with MeOH (50 mL), and filtrate
  11. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-f84c06e5a2754956b89943333b077a40
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812022B2

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