Water → 5-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

HRID 450447Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 450447
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.O.[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-].[Cs+].[Cs+]>CN(C=O)C>[CH3:17][N:18]1[CH:22]=[C:21]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:20]=[N:19]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 593227885-(2-Chloropyridin-4-yloxy)pyridin-2-amine

Produkt 1

HCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amineAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

5-(2-Chloropyridin-4-yloxy)pyridin-2-amine (0.47 g, 2.121 mmol) was dissolved in DMF (11 ml). Water (3.67 ml) was added to the mixture, followed by 1-methyl-4(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-pyrazole (0.662 g, 3.18 mmol), and cesium carbonate (2.63 g, 8.06 mmol). Argon was bubbled through the mixture for several minutes, and then palladium tetrakistriphenylphosphine (0.245 g, 0.212 mmol) was added. The flask was fitted with a condenser and argon was flushed through the system. The reaction mixture was then placed in a 90° C. oil bath under a balloon of argon and heated for 23 hours. The solution was then cooled to RT and diluted with THF (75 mL) and washed with brine (2×50 mL). The combined aqueous layers were then back extracted with THF (40 mL). The combined organic layers were dried (MgSO4), concentrated under reduced pressure and purified via silica gel chromatography (THF-ethyl acetate) to yield 5-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine as an off-white solid (0.357 g, 63% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.31 (d, 1H), 8.22 (s, 1H), 7.92 (s, 1H), 7.80 (d, 1H), 7.27 (dd, 1H), 7.14 (d, 1H), 6.85 (s, 6.57 (dd, 1H), 6.01 (s, 2H), 3.84 (s, 3H); MS (ESI) m/z: 268.1 (M+H+).

Aufarbeitung

  1. customArgon was bubbled through the mixture for several minutes
  2. customThe flask was fitted with a condenser
  3. customargon was flushed through the system
  4. customwas then placed in a 90° C.
  5. temperatureheated for 23 hours
  6. additiondiluted with THF (75 mL)
  7. washwashed with brine (2×50 mL)
  8. extractionThe combined aqueous layers were then back extracted with THF (40 mL)
  9. dry with materialThe combined organic layers were dried (MgSO4)
  10. concentrationconcentrated under reduced pressure
  11. custompurified via silica gel chromatography (THF-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-8b3751b6b37b4d218cf1a30a0eda9658
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486951B2

Notizen zur Reaktion

Wird geladen…