Sodium Carbonate → 5-Bromo-3-(4-fluorophenyl)pyrazin-2-amine

HRID 1929931Notes

Reaction equation

HRID 1929931 reaction equation
[NH2:1][C:2]1[C:7](Br)=[N:6][C:5]([Br:9])=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Br:9][C:5]1[N:6]=[C:7]([C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)[C:2]([NH2:1])=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 6200042-Amino-3,5-dibromopyrazine

Product 1

HCID 714639895-Bromo-3-(4-fluorophenyl)pyrazin-2-amine

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

Tetrakis (triphenylphosphine) palladium (0) (1.12 g, 0.97 mmol, 0.05 eq) was added portion-wise to a solution of 2-amino-3,5-dibromopyrazine (5.01 g, 19.76 mmol, 1.0 eq) in 1,2-dimethoxyethane (100 ml) at room temperature and the reaction stirred for 0.5 hours. A solution of sodium carbonate (5.30 g, 50.5 mmol, 2.6 eq) in water (50 ml) was added portion-wise to the resulting mixture, followed by 4-fluorophenylboronic acid (3.08 g, 21.9 mmol, 1.1 eq). The mixture was heated to 100° C. for 5 h. The resulting yellow solution was partitioned between 10% aqueous citric acid (25 ml) and ethyl acetate (50 ml). The organic layer was washed with 10% aqueous sodium bicarbonate (25 ml), brine (25 ml), dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel with a gradient of heptane to dichloromethane to afford 5-Bromo-3-(4-fluoro-phenyl)-pyrazin-2-ylamine as white crystals. Yield=3.22 g (60%). HPLC-MS=100%; 1.89 min (MW=268; M+1=270.1).

Workup

  1. customThe resulting yellow solution was partitioned between 10% aqueous citric acid (25 ml) and ethyl acetate (50 ml)
  2. washThe organic layer was washed with 10% aqueous sodium bicarbonate (25 ml), brine (25 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by chromatography on silica gel with a gradient of heptane to dichloromethane

Sources & evidence

ORD record
ord-3076cdbafc1547fcaabf1a0cd1c2890f
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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