Cesium carbonate → 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzonitrile

HRID 1472584Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1472584
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:10]=2[C:11]#[N:12])[C:5]([Cl:18])=[CH:4][N:3]=1.[CH3:19][C:20]1[CH:24]=[C:23]([NH2:25])[N:22]([CH:26]([CH3:28])[CH3:27])[N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:18][C:5]1[C:6]([NH:8][C:9]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:10]=2[C:11]#[N:12])=[CH:7][C:2]([NH:25][C:23]2[N:22]([CH:26]([CH3:28])[CH3:27])[N:21]=[C:20]([CH3:19])[CH:24]=2)=[N:3][CH:4]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 1210181-Isopropyl-3-methyl-1H-pyrazol-5-amineHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 575169182-[(2,5-Dichloro-4-pyridinyl)amino]-5-fluorobenzonitrile

Produkt 1

HCID 667695842-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzonitrileAusbeute 12,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Versuchsvorschrift

To a solution of 2-[(2,5-dichloro-4-pyridinyl)amino]-5-fluorobenzonitrile (7.09 g, 25.1 mmol) and 3-methyl-1-(1-methylethyl)-1H-pyrazol-5-amine (3.5 g, 25.1 mmol) in 1,4-dioxane (100 mL) was added cesium carbonate (24.58 g, 75 mmol) and the reaction mixture was degassed. DPEPhos (1.083 g, 2.012 mmol) was added followed by palladium acetate (0.226 g, 1.006 mmol) and the reaction mixture was heated to reflux overnight. The suspension was then filtered. The dioxane was evaporated off. The solid was purified by flash column chromatography on silica gel (10% DCM: EtOAC). Fractions were collected and evaporated. The yellow oil was dissolved in diethyl ether, sonicated and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzonitrile (1.3 g, 3.21 mmol, 12.76% yield) was isolated as a white solid; 1H NMR (400 MHz, METHANOL-d4) ppm 1.35 (d, J=6.82 Hz, 6 H) 2.20 (s, 3 H) 4.43 (quin, J=6.69 Hz, 1 H) 5.82 (s, 1 H) 5.89 (s, 1 H) 7.47-7.57 (m, 2 H) 7.61-7.74 (m, 1 H) 7.88 (s, 1 H); HPLC Rt=2.40 min, MS (ESI): 385.2 [M+H]+.

Aufarbeitung

  1. customthe reaction mixture was degassed
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux overnight
  4. filtrationThe suspension was then filtered
  5. customThe dioxane was evaporated off
  6. customThe solid was purified by flash column chromatography on silica gel (10% DCM: EtOAC)
  7. customFractions were collected
  8. customevaporated
  9. dissolutionThe yellow oil was dissolved in diethyl ether
  10. customsonicated
  11. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-475afb9a1b41435cab34aa5891f22f60
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012479B2

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