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

HRID 2233113Notes

Reaction equation

HRID 2233113 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([O:16][CH:17]([CH3:19])[CH3:18])=[N:14][CH:13]=[CH:12][N:11]3[CH:20]=2)=[CH:4][CH:3]=1.I[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([S:28][CH3:29])[N:23]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[C:15]([O:16][CH:17]([CH3:18])[CH3:19])=[N:14][CH:13]=[CH:12][N:11]3[C:20]=2[C:22]2[CH:27]=[CH:26][N:25]=[C:24]([S:28][CH3:29])[N:23]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 38589014-Iodo-2-(methylthio)pyrimidineHCID 57438775HCID 57438775, compound

Product 1

HCID 574387762-(4-Fluorophenyl)-8-isopropoxy-3-(2-methylsulfanylpyrimidin-4-yl)-imidazo[1,2-a]pyrazineYield 51.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Pd(OAc)2 (0.233 g, 1 mmol) was added to a degassed mixture of 2-(4-fluorophenyl)-8-isopropoxyimidazo[1,2-a]pyrazine (1.43 g, 5.2 mmol), 4-iodo-2-(methylthio)pyrimidine (Frontier, 1.96 g, 7.8 mmol), Cs2CO3 (2.57 g, 7.8 mmol) and PPh3 (0.54 g, 2 mmol) in DMF (6 mL). The resulting reaction mixture was heated at about 100° C. for about 4 h, cooled to ambient temperature, and partitioned between EtOAc and brine. The organic layer was separated, dried over MgSO4, filtered, and evaporated. The crude material was purified by silica gel chromatography using heptane/EtOAc (gradient, 100%/0% to 50%/50%) to afford 1.05 g (51%) of the title compound: LC/MS (Table 1, Method g) Rt=3.45 min; MS m/z: 396.2 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. temperaturecooled to ambient temperature
  3. custompartitioned between EtOAc and brine
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-8ddda15a76f04559870f4090c28c547a
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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