4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(2-Fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621944

Reaktionsgleichung

Reaktionsgleichung von HRID 1621944
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[F:10][C:11]1[C:16](B(O)O)=[CH:15][C:14]([O:20][CH3:21])=[CH:13][N:12]=1.C([O-])(=O)C.[K+]>CCO.O>[F:10][C:11]1[C:16]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[N:3]=2)=[CH:15][C:14]([O:20][CH3:21])=[CH:13][N:12]=1

Komponenten

6

Edukt 3

HCID 305914-Chloro-6-methyl-1,3,5-triazin-2-amineHCID 517044Potassium AcetateHCID 574973352-Fluoro-5-methoxypyridine-3-boronic acid

Produkt 1

HCID 666111694-(2-Fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a 20 mL microwave reaction tube was added 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9, 1.02 g, 7.05 mmol), 2-fluoro-5-methoxypyridin-3-ylboronic acid (1.67 g, 9.77 mmol), Am-Phos (Aldrich, 0.255 g, 0.360 mmol) and potassium acetate (Aldrich, 2.11 g, 21.5 mmol) in EtOH (10 mL) and water (1 mL). The mixture was degassed by bubbling argon through for 5 min. The tube was heated in a microwave reactor (Biotage) at 100° C. for 20 min. The reaction mixture was partitioned between water (200 mL) and EtOAc (200 mL). Layers were separated and insoluble material was collected (precipitate 1). The aqueous phase was further extracted with 10% isopropanol in chloroform (3×100 mL). Each organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. Upon addition of DCM to the crude product, precipitate came out and the solid was collected via filtration. The first precipitate (precipitate 1) and the solid from extraction were all desired product (1.17 g, 70.3%). 1H NMR (400 MHz, CDCl3) δ ppm 8.08 (dd, J=7.53, 3.23 Hz, 1H) 7.97 (dd, J=3.03, 1.86 Hz, 1H) 5.47 (br. s., 2H) 3.92 (s, 3H) 2.54 (s, 3H). m/z (ESI, positive ion): 236.0 (M+H)+.

Aufarbeitung

  1. customThe mixture was degassed
  2. customby bubbling argon through for 5 min
  3. customThe reaction mixture was partitioned between water (200 mL) and EtOAc (200 mL)
  4. customLayers were separated
  5. custominsoluble material was collected (precipitate 1)
  6. extractionThe aqueous phase was further extracted with 10% isopropanol in chloroform (3×100 mL)
  7. dry with materialEach organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionUpon addition of DCM to the crude product, precipitate
  11. filtrationthe solid was collected via filtration
  12. extractionThe first precipitate (precipitate 1) and the solid from extraction

Quellen und Nachweise

ORD-Eintrag
ord-f149619c22a147898e2d3d370d2dfc74
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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