Diisopropylethylamine → 5-Vinylpyrazin-2-amine

HRID 709308Notes

Reaction equation

HRID 709308 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[CH:9]([Sn](CCCC)(CCCC)CCCC)=[CH2:10].[Li+].[Cl-].CCN(C(C)C)C(C)C.[F-].[K+]>CN(C=O)C.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>[CH:9]([C:2]1[N:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1)=[CH2:10]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 81998TributylvinyltinHCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 5995392-Amino-5-bromopyrazine

Product 1

HCID 218972565-Vinylpyrazin-2-amineYield 77.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-bromopyrazin-2-amine (1.0 g, 5.78 mmol) and vinyltri-n-butyltin (2.01 g, 6.36 mmol) in DMF (19 mL) were added LiCl (269 mg, 6.36 mmol) and DIEA (1.1 mL, 6.36 mmol). After degassing for 20 minutes, Pd(PPh3)4 (400 mg, 0.35 mmol) was added to the reaction mixture. And then the mixture was refluxed for 4 hours under Ar atmosphere. The reaction mixture was cooled to room temperature and stirred with a 10% aqueous solution of potassium fluoride for 1 hour. The resulting solution was filtered through a pad of celite and washed with ethyl acetated. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (30% to 50% Ethyl acetate/Hexane) to afford title product (540 mg, 77% yield). MS m/z: 122 [M+1].

Workup

  1. customAfter degassing for 20 minutes
  2. temperatureAnd then the mixture was refluxed for 4 hours under Ar atmosphere
  3. filtrationThe resulting solution was filtered through a pad of celite
  4. washwashed with ethyl
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined organic layer was dried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by flash column chromatography (30% to 50% Ethyl acetate/Hexane)

Sources & evidence

ORD record
ord-d84e5a2694d241de8f7e477c0e8818ab
Source dataset
uspto-grants-2015_11
Patent number
US09180127B2

Reaction notes

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