Water → 3-chloro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

HRID 2279032Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2279032
[Cl:1][C:2]1[CH:3]=[C:4]([NH2:16])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11](Cl)[CH:10]=1.[CH3:17][N:18]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[N:19]1.C([O-])([O-])=O.[K+].[K+].O>COCCOC.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>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:21]2[CH:20]=[N:19][N:18]([CH3:17])[CH:22]=2)[CH:10]=1)[NH2:16]

Komponenten

7

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866416833-Chloro-4-(2-chloropyridin-4-yloxy)benzenamine

Produkt 1

HCID 673982863-chloro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamineAusbeute 104,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

3-Chloro-4-(2-chloropyridin-4-yloxy)benzenamine (0.89 g, 3.49 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazole (0.871 g, 4.19 mmol) and K2CO3 (1.302 g, 9.42 mmol) were combined in DME (6 mL)/H2O (7.5 mL) and the headspace was flushed with Ar for 10 min. Pd(Ph3P)4 (0.202 g, 0.174 mmol) was then added and the biphasic reaction was heated at 90° C. overnight. The mixture was cooled to RT and filtered to remove insoluble material. The filtrate was diluted with THF, washed with brine (3×) and the combined aqueous phases were back-extracted with THF (2×). The combined organics were washed with brine (1×), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (MeOH/CHCl3) to afford 3-chloro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (1.10 g, 83%). 1H NMR (400 MHz, DMSO-d6): δ 8.30-8.29 (m, 1 H), 8.22 (s, 1 H), 7.92 (s, 1 H), 7.12 (m, 1 H), 7.00-6.98 (m, 1 H), 6.72 (br s, 1 H), 6.58-6.54 (m, 1 H), 6.47-6.44 (m, 1 H), 5.44 (s, 2 H), 3.84 (s, 3H); MS (ESI) m/z: 301.1 (M+H+): 303.0 (M+2+H+).

Aufarbeitung

  1. customthe headspace was flushed with Ar for 10 min
  2. customthe biphasic reaction
  3. temperatureThe mixture was cooled to RT
  4. filtrationfiltered
  5. customto remove insoluble material
  6. additionThe filtrate was diluted with THF
  7. washwashed with brine (3×)
  8. extractionthe combined aqueous phases were back-extracted with THF (2×)
  9. washThe combined organics were washed with brine (1×)
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. custompurified by silica gel chromatography (MeOH/CHCl3)

Quellen und Nachweise

ORD-Eintrag
ord-f1d5532a93294184ac5fd5dee67513a3
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133183B2

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