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

HRID 2233076Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[N:14][CH:13]=[CH:12][N:11]3[CH:16]=2)=[CH:4][CH:3]=1.I[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[N:14][CH:13]=[CH:12][N:11]3[C:16]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-(4-fluorophenyl)imidazo[1,2-a]pyrazine (Preparation #2, 0.964 g, 4.52 mmol), 4-iodo-2-(methylthio)pyrimidine (Frontier, 2.28 g, 9.04 mmol), Cs2CO3 (2.21 g, 6.78 mmol), triphenylphosphine (0.474 g, 1.84 mmol), palladium acetate (0.203 g, 0.904 mmol), and DMF (10.5 mL) was heated at about 80° C. for about 13 h. The mixture was cooled to ambient temperature, diluted with water, and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting material was triturated with EtOAc and filtered to yield the title compound (0.640 g, 41%): LC/MS (Table 1, Method b) Rt=2.0 min; MS m/z: 338.4 (M+H)+.

Workup

temperatureThe mixture was cooled to ambient temperature
extractionextracted with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe resulting material was triturated with EtOAc
filtrationfiltered

Sources & evidence

ORD record: ord-3783aec60229429daa902845a2799693
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07709468B2

Reaction notes

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