Potassium Phosphate, Tribasic → 6-Chloro-3,8-bis(4-methylpyridin-3-yl)imidazo[1,2-b]pyridazine

HRID 2284363Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2284363
Br[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>[Cl:12][C:8]1[CH:9]=[C:10]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][C:14]=2[CH3:13])[C:5]2[N:6]([C:2]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:14]=3[CH3:13])=[CH:3][N:4]=2)[N:7]=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 866769426-Chloro-3,8-bis(4-methylpyridin-3-yl)imidazo[1,2-b]pyridazineAusbeute 24,7 %

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 (210 mg, 0.674 mmol), 4-methylpyridin-3-ylboronic acid (184 mg, 1.35 mmol), tetrakis(triphenylphosphine)palladium(0) (78 mg, 0.067 mmol), dioxane (6 mL), and K3PO4 (1 mL, 2.023 mmol) was stirred at room temperature for 5 min. under nitrogen. The resulting mixture was heated to 100° C. for 8 h in microwave. 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 prep. HPLC to give 56 mg (24%) product. 1H NMR (400 MHz, CD3OD) δ ppm 9.06 (1H, s), 8.93 (1H, s), 8.81 (2H, dd, J=15.23, 5.92 Hz), 8.17 (1H, s), 7.96-8.13 (2H, m), 7.68 (1H, s), 2.65 (3H, s), 2.58 (3H, s); LC/MS: Rt=0.88 min. LC/MS (Condition A): 336.14/338.15.

Aufarbeitung

  1. temperatureThe resulting mixture was heated to 100° C. for 8 h in microwave
  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 prep

Quellen und Nachweise

ORD-Eintrag
ord-f815b891e2fb4c918cdffbbdda16acae
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145419B2

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