Potassium Carbonate → 5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amine

HRID 1049273Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1049273
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:16][N:17]1[CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=[N:18]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[CH3:16][N:17]1[CH:21]=[C:20]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[N:11][C:12]([NH2:15])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:19]=[N:18]1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 904034955-((2-Chloropyridin-4-yl)oxy)pyrimidin-2-amine

Produkt 1

HCID 904034835-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amineAusbeute 55,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

5-((2-chloropyridin-4-yl)oxy)pyrimidin-2-amine (676 mg, 3.04 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (758 mg, 3.64 mmol), potassium carbonate (1.259 g, 9.11 mmol) and Pd(PPh3)4 (175 mg, 0.152 mmol) were combined in dioxane (12 mL) and water (3 mL). The mixture was degassed with argon, and warmed to 85° C. overnight. The mixture was diluted with EtOAc (75 mL) and water (40 mL) and was filtered to collect an off-white solid. The organic phase was separated, washed with brine (40 mL) and evaporated at reduced pressure to give additional off-white solid. The two crops of solids were combined and triturated with EtOAc (15 mL) with sonication. The solid was collected by filtration, washed with EtOAc (2×5 mL) and dried under vacuum to provide 5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amine (455 mg, 55%). 1H NMR (DMSO-d6): δ 8.34 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 8.22 (s, 2H), 7.96 (s, 1H), 7.19 (d, J=2.4 Hz, 1H), 6.77 (s, 2H), 6.67 (dd, J=5.7, 2.5 Hz, 1H), 3.84 (s, 3H); MS (ESI) m/z: 269.1 (M+H+).

Aufarbeitung

  1. customThe mixture was degassed with argon
  2. additionThe mixture was diluted with EtOAc (75 mL) and water (40 mL)
  3. filtrationwas filtered
  4. customto collect an off-white solid
  5. customThe organic phase was separated
  6. washwashed with brine (40 mL)
  7. customevaporated at reduced pressure
  8. customto give additional off-white solid
  9. customtriturated with EtOAc (15 mL) with sonication
  10. filtrationThe solid was collected by filtration
  11. washwashed with EtOAc (2×5 mL)
  12. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-4126eb3fe298440ebe9346e9301f3003
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09382228B2

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