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

HRID 450421Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 450421
[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]([NH2:16])[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

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 stirred with heating at 90° C. overnight. The reaction was cooled to RT and filtered to remove insoluble material. The filtrate was diluted with THF and washed with brine (3×). The combined aqueous phases were extracted with THF (2×). The combined organics were washed with brine (1×), dried (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-yloxy)benzenamine (1.10 g, 83% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.30-8.29 (m, 1H), 8.22 (s, 1H), 7.92 (s, 1H), 7.12 (m, 1H), 7.00-6.98 (m, 1H), 6.72 (br s, 1H), 6.58-6.54 (m, 1H), 6.47-6.44 (m, 1H), 5.44 (s, 2H), 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 reaction 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 extracted with THF (2×)
  9. washThe combined organics were washed with brine (1×)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. custompurified by silica gel chromatography (MeOH/CHCl3)

Quellen und Nachweise

ORD-Eintrag
ord-79d174f646b84366a6088a5091e7c23c
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486951B2

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