Dimethylformamide → 2-(5-Aminopyrazin-2-ylthio)ethanol

HRID 1663015Notes

Reaction equation

HRID 1663015 reaction equation
[SH:1][CH:2](O)C.[NH2:5][C:6]1[CH:11]=[N:10][C:9](Br)=[CH:8][N:7]=1.CN(C)[CH:15]=[O:16]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:5][C:6]1[N:7]=[CH:8][C:9]([S:1][CH2:2][CH2:15][OH:16])=[N:10][CH:11]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 5995392-Amino-5-bromopyrazineHCID 4713212Mercapto-ethanol

Product 1

HCID 583285082-(5-Aminopyrazin-2-ylthio)ethanolYield 44%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

Based on the method described in WO2004/052869, mercaptoethanol (0.93 mL) and tetrakis(triphenylphosphine)palladium (3.39 g) were added to a solution of 1.00 g of 2-amino-5-bromopyrazine (5.75 mmol) in N,N-dimethylformamide (15.1 mL), and the resulting mixture was heated and stirred in a sealed tube for about 3 hours at 120° C. After cooling, the reaction mixture was diluted with water, and then extracted (100 mL×6) with a mixed liquid (methylene chloride:ethanol=5:1). The organic layer was dried over anhydrous sodium sulfate, then filtered, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography (hexane:ethyl acetate=1:1, then ethyl acetate, and then ethyl acetate:methanol=10:1), then recrystallized (chloroform) to obtain 470 mg of the title compound (yield 44%) as yellow needle-like crystals.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureAfter cooling
  3. extractionextracted (100 mL×6) with a mixed liquid (methylene chloride:ethanol=5:1)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed by distillation under reduced pressure
  7. customThe resulting residue was purified by column chromatography (hexane
  8. customethyl acetate=1:1, then ethyl acetate, and then ethyl acetate:methanol=10:1), then recrystallized (chloroform)

Sources & evidence

ORD record
ord-8122365d78684e0380d00a477ee81a8c
Source dataset
uspto-grants-2011_10
Patent number
US08034819B2

Reaction notes

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