Cesium carbonate → 2-(4-Fluorophenyl)-8-methyl-3-(2-methylsulfanylpyrimidin-4-yl)-imidazo[1,2-a]pyrazine

HRID 2233086Notes

Reaction equation

HRID 2233086 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[N:14][CH:13]=[CH:12][N:11]3[CH:17]=2)=[CH:4][CH:3]=1.I[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([S:25][CH3:26])[N:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>O.CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[N:14][CH:13]=[CH:12][N:11]3[C:17]=2[C:19]2[CH:24]=[CH:23][N:22]=[C:21]([S:25][CH3:26])[N:20]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 38589014-Iodo-2-(methylthio)pyrimidineHCID 57438749HCID 57438749, compound

Product 1

HCID 574387482-(4-Fluorophenyl)-8-methyl-3-(2-methylsulfanylpyrimidin-4-yl)-imidazo[1,2-a]pyrazineYield 58.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Into a flask was added 2-(4-fluorophenyl)-8-methylimidazo[1,2-a]pyrazine (Preparation #K.1; 4.8 g, 21.0 mmol), 4-iodo-2-(methylthio)pyrimidine (Frontier, 9.4 g, 31.7 mmol), Cs2CO3 (10.3 g, 31.7 mmol), PPh3 (2.2 g, 8.4 mmol), and DMF (50 mL). The mixture was degassed under vacuum and back-filled with N2. The mixture was charged with Pd(OAc)2 (0.95 g, 4.2 mmol) and heated at about 100° C. for about 16 h. The mixture was cooled to ambient temperature, diluted with water (200 mL), and extracted with DCM (3×200 mL). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (0-5% MeOH:DCM) followed by trituration in EtOAc yielded the title compound (4.30 g, 58% yield): LC/MS (Table 1, Method b) Rt=2.2 min; MS m/z: 352.3 (M+H)+.

Workup

  1. customThe mixture was degassed under vacuum
  2. additionback-filled with N2
  3. temperatureThe mixture was cooled to ambient temperature
  4. extractionextracted with DCM (3×200 mL)
  5. washThe combined organic layers were washed with brine (200 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash column chromatography (0-5% MeOH:DCM)

Sources & evidence

ORD record
ord-ae3eaa1cdcd64e19adad2ed90c567608
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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