Potassium Phosphate, Tribasic → Methyl 4-(imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxylate

HRID 2046402Notes

Reaction equation

HRID 2046402 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.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([CH3:29])=[CH:18][C:19]=1B1OC(C)(C)C(C)(C)O1)=[O:14].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:18]2[CH:19]=[C:15]([C:13]([O:12][CH3:11])=[O:14])[S:16][C:17]=2[CH3:29])[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 46702783Methyl 5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate

Product 1

HCID 58046374Methyl 4-(imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxylate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

3-Bromoimidazo[1,2-b]pyridazine (0.40 g, 2.02 mmol), methyl-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate (0.86 g, 3.03 mmol), Pd2(dba)3 (0.19 g, 0.20 mmol), tricyclohexylphosphine (0.14 g, 0.51 mmol), aqueous tribasic potassium phosphate (1.27 M, 1.45 mL, 6.85 mmol), and 1,4-dioxane (10.1 mL) were placed in a flask and purged with nitrogen for five minutes. The solution was heated to 100° C. for four hours. The solution was cooled to room temperature, poured into an aqueous solution of saturated sodium bicarbonate, and extracted with ethyl acetate (×3). The combined organic layers were dried with magnesium sulfate, filtered, and concentrated and the residue purified by flash chromatography to afford the title compound as a yellow solid. 1H NMR (500 MHz, CD3SOCD3) δ 8.62 (d, 1H); 8.24 (s, 1H); 8.21 (d, 1H); 8.06 (s, 1H); 7.30 (dd, 1H); 3.83 (s, 3H); 2.58 (s, 3H). LRMS (APCI) calc'd for (C13H11N3O2S) [M+H]+, 274.0. found 274.0.

Workup

  1. custompurged with nitrogen for five minutes
  2. temperatureThe solution was cooled to room temperature
  3. additionpoured into an aqueous solution of saturated sodium bicarbonate
  4. extractionextracted with ethyl acetate (×3)
  5. dry with materialThe combined organic layers were dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-c14b9daa6c6641fd9eed24d5ea36888a
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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