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

HRID 1472587

Reaktionsgleichung

Reaktionsgleichung von HRID 1472587
Cl[C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:12]=1[C:13]#[N:14].[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].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.[CH3:77][C:78]1[CH:82]=[C:81]([NH2:83])[N:80]([CH:84]([CH3:86])[CH3:85])[N:79]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:9][C:5]1[C:6]([NH:10][C:11]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:12]=2[C:13]#[N:14])=[CH:7][C:2]([NH:83][C:81]2[N:80]([CH:84]([CH3:86])[CH3:85])[N:79]=[C:78]([CH3:77])[CH:82]=2)=[N:3][CH:4]=1

Komponenten

9

Edukt 6

HCID 10796Cesium carbonateHCID 61695Pentapotassium TriphosphateHCID 1210181-Isopropyl-3-methyl-1H-pyrazol-5-amineHCID 27833922-Amino-3-fluorobenzonitrileHCID 4285986Bis[2-(diphenylphosphino)phenyl] ether2×HCID 534009652,5-Dichloro-4-iodopyridine

Produkt 1

HCID 667697122-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzonitrileAusbeute 53,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysator2×HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a degassed solution of 2,5-dichloro-4-iodopyridine (8 g, 29.2 mmol), 2-amino-3-fluorobenzonitrile (3.98 g, 29.2 mmol) and potassium triphosphate (18.60 g, 88 mmol) in 1,4-dioxane (60 ml) stirred under nitrogen at the room temperature was added DPEPhos (1.258 g, 2.337 mmol) and palladium acetate (0.262 g, 1.168 mmol) The reaction mixture was stirred at reflux for 18 hr. The reaction mixture was filtered. 3-Methyl-1-(1-methylethyl)-1H-pyrazol-5-amine (4.07 g, 29.2 mmol) and cesium carbonate (28.6 g, 88 mmol) were added. The reaction mixture was degassed and palladium acetate (0.262 g, 1.168 mmol) and DPEPhos (1.258 g, 2.337 mmol) were added. The reaction mixture was refluxed overnight. The reaction mixture was filtered and the solid was dissolved in water, heated to 50° C. and stirred for 10 minutes, then filtered again. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzonitrile (6 g, 15.59 mmol, 53.4% yield) was isolated as an orange solid. 1H NMR (400 MHz, DMSO-d6) d ppm 1.23 (d, J=6.57 Hz, 6 H) 2.07 (s, 3 H) 4.32 (quin, J=6.57 Hz, 1 H) 5.64 (d, J=2.02 Hz, 1 H) 5.83 (s, 1 H) 7.39-7.58 (m, 1 H) 7.63-7.82 (m, 2 H) 7.88 (s, 1 H) 8.26 (br. s., 1 H) 8.41 (br. s., 1 H); HPLC Rt=2.35 min, MS (ESI): 385.0 [M+H]+.

Aufarbeitung

  1. temperatureat reflux for 18 hr
  2. filtrationThe reaction mixture was filtered
  3. customThe reaction mixture was degassed
  4. temperatureThe reaction mixture was refluxed overnight
  5. filtrationThe reaction mixture was filtered
  6. dissolutionthe solid was dissolved in water
  7. stirringstirred for 10 minutes
  8. filtrationfiltered again

Quellen und Nachweise

ORD-Eintrag
ord-0bb17afb07d0499eb309a45924f6861d
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012479B2

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