Cesium carbonate → 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-N,6-dimethoxy-benzamide

HRID 1045971

Reaktionsgleichung

Reaktionsgleichung von HRID 1045971
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[NH2:43][C:44]1[CH:54]=[CH:53][CH:52]=[C:51]([O:55][CH3:56])[C:45]=1[C:46]([NH:48][O:49][CH3:50])=[O:47].[CH3:57][N:58]1[CH:62]=[C:61]([NH:63][C:64]2[CH:69]=[C:68](I)[C:67]([C:71]([F:74])([F:73])[F:72])=[CH:66][N:65]=2)[C:60]([CH3:75])=[N:59]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:57][N:58]1[CH:62]=[C:61]([NH:63][C:64]2[CH:69]=[C:68]([NH:43][C:44]3[CH:54]=[CH:53][CH:52]=[C:51]([O:55][CH3:56])[C:45]=3[C:46]([NH:48][O:49][CH3:50])=[O:47])[C:67]([C:71]([F:73])([F:72])[F:74])=[CH:66][N:65]=2)[C:60]([CH3:75])=[N:59]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 56951658N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amineHCID 569516592-amino-N,6-dimethoxybenzamide

Produkt 1

HCID 569514302-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-N,6-dimethoxy-benzamideAusbeute 74,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (34.1 mg, 0.06 mmol), palladium(II) acetate (7.93 mg, 0.04 mmol), 2-amino-N,6-dimethoxybenzamide (131 mg, 0.67 mmol), N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol) and cesium carbonate (256 mg, 0.79 mmol) were weighed out in a microwave vial, sealed and dioxane (5 mL) was added. Argon was bubbled through the mixture for 5 minutes. The reaction was stirred at 90° C. overnight. The reaction mixture was allowed to cool to room temperature, diluted with DCM and MeOH. Silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel (25 g) eluting with 0 to 5% MeOH in EtOAc/DCM (1:1). The solvent was evaporated to dryness. The residue was triturated in Et2O and the resulting precipitate was collected by filtration, washed with Et2O and dried to a constant weight to afford the title compound (131 mg, 74.1%) as a off-white solid. NMR Spectrum: (DMSOd6) 2.04 (s, 3H), 3.62 (s, 3H), 3.69 (s, 3H), 3.81 (s, 3H), 6.31 (bs, 1H), 6.89 (d, 1H), 7.06 (d, 1H), 7.43 (dd, 1H), 7.79 (s, 1H), 7.86 (s, 1H), 8.14 (s, 1H), 8.38 (s, 1H), 11.38 (s, 1H); Mass spectrum: MH+ 451.

Aufarbeitung

  1. customsealed
  2. customArgon was bubbled through the mixture for 5 minutes
  3. temperatureto cool to room temperature
  4. additiondiluted with DCM and MeOH
  5. additionSilica gel was added
  6. concentrationthe mixture was concentrated
  7. customThe crude product was purified by flash chromatography on silica gel (25 g)
  8. washeluting with 0 to 5% MeOH in EtOAc/DCM (1:1)
  9. customThe solvent was evaporated to dryness
  10. customThe residue was triturated in Et2O
  11. filtrationthe resulting precipitate was collected by filtration
  12. washwashed with Et2O
  13. customdried to a constant weight

Quellen und Nachweise

ORD-Eintrag
ord-29ecec3a8feb4107abcc31cb6d6e50db
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569298B2

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