Potassium Phosphate, Tribasic → Methyl 4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxylate

HRID 2046405Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2046405
Br[C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C[C:12]1[S:16][C:15]([C:17]([O:19][CH3:20])=[O:18])=[CH:14][C:13]=1B1OC(C)(C)C(C)(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[N:4]1[CH:3]=[C:2]([C:13]2[CH:14]=[C:15]([C:17]([O:19][CH3:20])=[O:18])[S:16][CH:12]=2)[N:6]2[C:5]=1[CH:10]=[CH:9][CH:8]=[N:7]2

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 128723193-Bromoimidazo(1,2-b)pyridazineHCID 46703107Methyl 5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate

Produkt 1

HCID 58046452Methyl 4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

3-Bromoimidazo[1,2-b]pyridazine (700 mg, 3.53 mmol), methyl 5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate (1.04 g, 3.89 mmol), Pd2(dba)3 (324 mg, 0.353 mmol), tricyclohexylphosphine (248 mg, 0.884 mmol), aqueous tribasic potassium phosphate (2.54 mL, 12.0 mmol, 1.27 M), and 1,4-dioxane (17.7 mL) were placed in a sealed tube and purged with nitrogen for 5 minutes. The solution was heated to 100° C. for 1.5 h, after which the reaction was cooled to room temperature. Saturated aqueous sodium bicarbonate was added to the mixture. The aqueous layer was then extracted with ethyl acetate (×3). The combined organic layers were then dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography affording the title compound as a yellow solid. 1H NMR (500 MHz, CD3SOCD3) δ 8.70 (d, 1H); 8.68 (s, 1H); 8.54 (s, 1H); 8.42 (s, 1H); 8.22 (d, 1H); 7.31 (dd, 1H); 3.86 (s, 3H). LRMS (APCI) calc'd for (C12H9N3O2S) [M+H]+, 260.0. found 260.0.

Aufarbeitung

  1. custompurged with nitrogen for 5 minutes
  2. temperatureafter which the reaction was cooled to room temperature
  3. additionSaturated aqueous sodium bicarbonate was added to the mixture
  4. extractionThe aqueous layer was then extracted with ethyl acetate (×3)
  5. dry with materialThe combined organic layers were then dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-690c1d1acc3142498d64c2d0e60d53df
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08592425B2

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