Methyl 3-aminopyrazinecarboxylate → Methyl 2-(4-fluorophenyl)imidazo[1,2-a]pyrazine-8-carboxylate

HRID 2233074Notes

Reaction equation

HRID 2233074 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=O.[NH2:12][C:13]1[C:14]([C:19]([O:21][CH3:22])=[O:20])=[N:15][CH:16]=[CH:17][N:18]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.C(Cl)Cl>[CH3:22][O:21][C:19]([C:14]1[C:13]2[N:18]([CH:2]=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=3)[N:12]=2)[CH:17]=[CH:16][N:15]=1)=[O:20]

Participants

6

Reactant 3

HCID 72669Methyl 3-aminopyrazinecarboxylateHCID 967492-Bromo-1-(4-fluorophenyl)ethan-1-oneHCID 516892Sodium Bicarbonate

Product 1

HCID 57438736Methyl 2-(4-fluorophenyl)imidazo[1,2-a]pyrazine-8-carboxylateYield 80.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-bromo-1-(4-fluorophenyl)ethanone (30.0 g, 138 mmol) and methyl 3-aminopyrazine-2-carboxylate (21.2 g, 138 mmol) in DMF (200 mL) was heated at about 80° C. for about 16 h. The mixture was allowed to cool to ambient temperature and was neutralized with saturated aqueous NaHCO3. The mixture was diluted with DCM. The layers were separated and the aqueous layer was washed with DCM. The combined organic layers were washed with brine, dried over MgSO4, and eluted through a silica gel plug with EtOAc as the eluent. The combined organic layers were concentrated under reduced pressure to yield 30 g black oil. The material was diluted with DCM and the insoluble materials were removed by filtration to yield 2.0 g of the title compound. A second crop was obtained similarly to yield 1.8 g. The remaining filtrate was purified by flash silica gel chromatography using EtOAc as an eluent to yield an additional 3.1 g of the title compound (6.9 g, 15%): LC/MS (Table 1, Method b) Rt=1.7 min; MS m/z: 272.3 (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. customThe layers were separated
  3. washthe aqueous layer was washed with DCM
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. washeluted through a silica gel plug with EtOAc as the eluent
  7. concentrationThe combined organic layers were concentrated under reduced pressure

Sources & evidence

ORD record
ord-488512b184e9404d93189290abe5f787
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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