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

HRID 2046405Notes

Reaction equation

HRID 2046405 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-690c1d1acc3142498d64c2d0e60d53df
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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