Cesium carbonate → 6-(2,4-Difluorophenyl)-5-(2-(methylthio)pyrimidin-5-yl)imidazo[2,1-b]oxazole

HRID 1930089Notes

Reaction equation

HRID 1930089 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1I)[CH:14]=[CH:13][O:12]2.[CH3:18][S:19][C:20]1[N:25]=[CH:24][C:23](B(O)O)=[CH:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:23]1[CH:22]=[N:21][C:20]([S:19][CH3:18])=[N:25][CH:24]=1)[CH:14]=[CH:13][O:12]2

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27632632-(Methylthio)pyrimidine-5-boronic acidHCID 594578066-(2,4-Difluorophenyl)-5-iodoimidazo[2,1-b]oxazole

Product 1

HCID 579298716-(2,4-Difluorophenyl)-5-(2-(methylthio)pyrimidin-5-yl)imidazo[2,1-b]oxazoleYield 68.6%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A round bottom flask was charged with 6-(2,4-difluorophenyl)-5-iodoimidazo[2,1-b]oxazole (0.25 g, 0.72 mmol; Example #8, step C) and 2-(methylthio)pyrimidin-5-ylboronic acid (0.184 g, 1.08 mmol, Indofine), bis(triphenylphosphine)palladium (II) chloride (0.051 g, 0.072 mmol) and cesium carbonate (0.588 g, 1.81 mmol). The reaction mixture was diluted with 1,4-dioxane (10 mL) and water (2 mL). The reaction mixture was degassed under vacuum and purged with nitrogen 3 times and then stirred at about 90° C. for about 4 h. The reaction mixture was cooled to ambient temperature and then diluted with H2O. The mixture was extracted with EtOAc (2×200 mL). The organic layers were combined and concentrated under reduced pressure. The product was purified by silica gel flash chromatography using a gradient of 0-10% EtOAc in DCM to give the title compound as yellow solid (0.17 g, 64%); 1H NMR (DMSO-d6) δ 8.62 (s, 2H), 8.34 (d, J=1.8, 1H), 8.12 (d, J=1.8, 1H), 7.68 (m, 1H), 7.33-7.25 (m, 1H), 7.20 (m, 1H), 2.54 (s, 3H).

Workup

  1. customThe reaction mixture was degassed under vacuum
  2. custompurged with nitrogen 3 times
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. additiondiluted with H2O
  5. extractionThe mixture was extracted with EtOAc (2×200 mL)
  6. concentrationconcentrated under reduced pressure
  7. customThe product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-bf2e0b792f17459b954410e8e768f05f
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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