Tetrahydrofuran → HCID 58557512, compound

HRID 1969535Notes

Reaction equation

HRID 1969535 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Br:8])[N:7]=1.[CH2:10]1[CH2:14]OC[CH2:11]1>[Cu]I.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:8][C:6]1[N:7]=[C:2]([C:11]#[C:10][CH3:14])[C:3]([NH2:9])=[N:4][CH:5]=1

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 6200042-Amino-3,5-dibromopyrazine

Product 1

HCID 58557512HCID 58557512, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalyst

Conditions

Temperature
0 °C

Procedure

To a solution of 3,5-dibromopyrazin-2-amine (10.0 g, 39.5 mmol) in THF (200 mL) was added copper (I) iodide (0.377 g, 1.98 mmol), bis(triphenylphosphine)palladium (II) dichloride (1.39 g, 1.98 mmol) and TEA (16.5 mL, 119 mmol). The reaction mixture was cooled to about 0° C. and degassed with Ar. The reaction mixture was stirred for about 5 min and then the reaction mixture was sparged with propyne and a propyne atmosphere was maintained via balloon. The reaction mixture was stirred for about 30 min at about 0° C. and then was allowed to warm to ambient temperature. The reaction mixture was stirred for about 2 h and then EtOAc (100 mL) and water (100 mL) were added to the reaction mixture. The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concd in vacuo. The crude mixture was purified by chromatography on silica gel (120 g) eluting with 10-60% EtOAc in DCM (dry loaded) to provide 5-bromo-3-(prop-1-ynyl)pyrazin-2-amine (7.05 g, 84%) as a yellow solid: LC/MS (Table 1, Method a) Rt=1.79 min; MS m/z: 212, 214 (1:1) (M+H)+.

Workup

  1. customdegassed with Ar
  2. customthe reaction mixture was sparged with propyne
  3. temperaturea propyne atmosphere was maintained via balloon
  4. stirringThe reaction mixture was stirred for about 30 min at about 0° C.
  5. temperatureto warm to ambient temperature
  6. stirringThe reaction mixture was stirred for about 2 h
  7. additionEtOAc (100 mL) and water (100 mL) were added to the reaction mixture
  8. customThe organic layer was separated
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. customThe crude mixture was purified by chromatography on silica gel (120 g)
  12. washeluting with 10-60% EtOAc in DCM (dry loaded)

Sources & evidence

ORD record
ord-4a8879513c544b678b709e548e686535
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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