Sodium Carbonate → 2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

HRID 1098542

Reaktionsgleichung

Reaktionsgleichung von HRID 1098542
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([F:16])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:17][N:18]1[CH:22]=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[N:19]1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:16][C:11]1[CH:10]=[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:21]3[CH:20]=[N:19][N:18]([CH3:17])[CH:22]=3)[CH:7]=2)[CH:14]=[CH:13][C:12]=1[NH2:15]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 27600771-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 594583014-(2-Chloropyridin-4-yloxy)-2-fluorobenzenamine

Produkt 1

HCID 594583192-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamineAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of 4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamine (3 g, 12.6 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (5.2 g, 25.2 mmol), and Na2CO3 (2.7 g, 25.2 mmol) in DME (18 mL) and water (6 mL) was sparged with nitrogen for 20 min. Pd(PPh3)4 (729 mg, 0.63 mmol) was added and the resulting mixture was heated to 100° C. for 16 h. The solvent was removed under reduced pressure and the crude product was suspended in water and extracted with EtOAc. The organic layer was washed with brine, dried (NaSO4), filtered, concentrated in vacuo and purified via silica gel chromatography to give 2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine (2 g, 56% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.31 (d, J=5.7 Hz, 1 H), 8.21 (s, 1 H), 7.92 (s, 1 H), 7.12 (d, J=2.4 Hz, 1 H), 6.96 (m, 1 H), 6.85-6.72 (m, 2 H), 6.56 (m, 1 H), 5.15 (s, 2 H), 3.84 (s, 3H); MS (ESI) m/z: 285.0 (M+H+).

Aufarbeitung

  1. customThe solvent was removed under reduced pressure
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried (NaSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-94ce00747cab4569aa9ca9362424a55c
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143293B2

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