Sodium Carbonate → 5-(Thiophen-3-yl)pyrazin-2-amine

HRID 720001Notes

Reaction equation

HRID 720001 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][C:11](B(O)O)=[CH:10]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(O)C.C(OCC)(=O)C.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][C:11]([C:5]2[N:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=2)=[CH:10]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 581760Thiophene-3-boronic acidHCID 5995392-Amino-5-bromopyrazine

Product 1

HCID 116512355-(Thiophen-3-yl)pyrazin-2-amineYield 69%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 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), 3-thiopheneboronic acid (500 mg, 3.908 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 for 45 min. The reaction mixture was then cooled, diluted with ethyl acetate, and washed with water and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 1/1 hexanes/ethyl acetate) afforded 5-thiophen-3-yl-pyrazin-2-ylamine (351.3 mg, 69%) as a light purple solid: EI-HRMS m/e calcd for C8H7N3S (M+) 177.0361, found 177.0358.

Workup

  1. temperatureunder reflux for 45 min
  2. temperatureThe reaction mixture was then cooled
  3. washwashed with water
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ec7d06e4bd9240bb9bb9468fed880497
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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