Potassium Phosphate, Tribasic → HCID 86676940, Verbindung

HRID 2284361

Reaktionsgleichung

Reaktionsgleichung von HRID 2284361
[Br:1][C:2]1[N:6]2[N:7]=[C:8]([Cl:12])[CH:9]=[C:10](Br)[C:5]2=[N:4][CH:3]=1.[CH3:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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.O1CCOCC1>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([Cl:12])[CH:9]=[C:10]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:14]=3[CH3:13])[C:5]2=[N:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27627114-Methylpyridine-3-Boronic AcidHCID 446307233,8-Dibromo-6-chloroimidazo[1,2-b]pyridazine

Produkt 1

HCID 86676940HCID 86676940, VerbindungAusbeute 30,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A microwave vial was charged with a mixture of 3,8-dibromo-6-chloroimidazo[1,2-b]pyridazine (1.0 g, 3.21 mmol), 4-methylpyridin-3-ylboronic acid (0.440 g, 3.21 mmol), tetrakis(triphenylphosphine)palladium(0) (0.371 g, 0.321 mmol), dioxane (16 mL), and K3PO4 (4.82 mL, 9.64 mmol) (2.0 M solution in water) was stirred at room temperature for 5 min. under nitrogen. The resulting mixture was heated to 100° C. for 4 h in a microwave heater. The reaction mixture was cooled to room temperature, quenched with water, and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by BIOTAGE® (20-80% EtOAc/CH2Cl2, 1.5 L, then 20%-65% B/CH2Cl2 (0.9 L); B: 10% MeOH/CH2Cl2) to give 320 mg (15.4%) product. 1H NMR (400 MHz, CD3OD) δ ppm 8.91 (1H, s), 8.82 (1H, d, J=5.79 Hz), 8.04 (1H, d, J=5.79 Hz), 7.88 (1H, s), 7.57 (1H, s), 2.54 (3H, s). LC (Conditions B & C): >95% purity; LC/MS: Rt=1.47 min. LC/MS (Condition A): 322.96/324.96.

Aufarbeitung

  1. temperatureThe resulting mixture was heated to 100° C. for 4 h in a microwave heater
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with water
  4. additiondiluted with EtOAc
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by BIOTAGE® (20-80% EtOAc/CH2Cl2, 1.5 L

Quellen und Nachweise

ORD-Eintrag
ord-cfc3dec3da474bb2b1a9bf751b285d43
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145419B2

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