Triethylamine → HCID 86667832, compound

HRID 869033Notes

Reaction equation

HRID 869033 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1)#[CH:2].Br[C:11]1[C:12]([NH2:18])=[N:13][CH:14]=[C:15]([Br:17])[N:16]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O.[Cl-].[Na+].O.[Cu]I.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>[NH2:18][C:12]1[C:11]([C:2]#[C:1][C:3]2[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=2)=[N:16][C:15]([Br:17])=[CH:14][N:13]=1

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 139144m-EthynylphenolHCID 6200042-Amino-3,5-dibromopyrazine

Product 1

HCID 86667832HCID 86667832, compoundYield 71%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

3-Ethynylphenol (560.5 mg, 310.9 μL, 4.745 mmol) was added dropwise to a solution of 3,5-dibromopyrazin-2-amine (1 g, 3.954 mmol), triethylamine (4.001 g, 5.511 mL, 39.54 mmol), copper (I) iodide (90.37 mg, 0.4745 mmol) and Pd(PPh3)4 (228.5 mg, 0.1977 mmol) in DMF (10 mL) and the resulting solution heated at 120° C. for 3 hours. The reaction mixture was cooled to ambient temperature and diluted with EtOAc and 1 MHCl/brine (1/1) and the layers separated. The aqueous layer was extracted with EtOAc (×2) and the combined organic extracts washed with brine (×2), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 120 g column, eluting with 0 to 40% EtOAc/Petroleum Ether, dry loaded) to give the sub-title product as a yellow solid (815 mg, 71% Yield). 1H NMR (400.0 MHz, DMSO) δ 6.88 (dd, 1H), 7.00 (br s, 2H), 7.11-7.11 (m, 1H), 7.17 (d, 1H), 7.25 (t, 1H), 8.12 (s, 1H) and 9.77 (s, 1H) ppm; MS (ES+) 292.0.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (×2)
  4. washthe combined organic extracts washed with brine (×2)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ISCO Companion™, 120 g column, eluting with 0 to 40% EtOAc/Petroleum Ether, dry loaded)

Sources & evidence

ORD record
ord-434791d2f6c8483e8971ab045ad6d4c0
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

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