Sodium Chloride → 2-Pyrazinamine, 5-(2-thienyl)-

HRID 719999Notes

Reaction equation

HRID 719999 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][C:5](Br)=[CH:4][N:3]=1.[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+]>COCCOC.C(O)C.C(OCC)(=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:5]1[N:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=1

Participants

10

Reactant 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 5995392-Amino-5-bromopyrazineHCID 27339602-Thiopheneboronic acid

Product 1

HCID 116440152-Pyrazinamine, 5-(2-thienyl)-Yield 52.4%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-amino-5-bromopyrazine (500 mg, 2.874 mmol), dichlorobis(triphenylphosphine)palladium(II) (290 mg, 0.413 mmol), 2-thiopheneboronic acid (500 mg, 3.907 mmol), and a saturated aqueous sodium carbonate solution (4 mL) in ethylene glycol dimethyl ether (8 mL) and ethanol (8 mL) was heated under reflux overnight. The reaction mixture was cooled, diluted with ethyl acetate, water, and a saturated aqueous sodium chloride solution. After mixing, the layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica 1/1 hexanes/ethyl acetate) afforded 5-thiophen-2-yl-pyrazin-2-ylamine (267 mg, 52.4%) as a yellow solid: EI-HRMS m/e calcd for C8H7N3S (M+) 177.0361, found 177.0355.

Workup

  1. temperatureunder reflux overnight
  2. temperatureThe reaction mixture was cooled
  3. additionAfter mixing
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d8b66c322b9c403eaa486bb975e6e305
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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