Triethylamine → HCID 54670657, compound

HRID 869029Notes

Reaction equation

HRID 869029 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]([NH2:29])=[N:13][CH:14]=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH:26]([CH3:28])[CH3:27])(=[O:25])=[O:24])=[CH:19][CH:18]=2)[N:16]=1.CCN(CC)CC>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>[NH2:29][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]([C:17]2[CH:18]=[CH:19][C:20]([S:23]([CH:26]([CH3:28])[CH3:27])(=[O:25])=[O:24])=[CH:21][CH:22]=2)=[CH:14][N:13]=1

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 139144m-EthynylphenolHCID 580843723-Bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine

Product 1

HCID 54670657HCID 54670657, compoundYield 68%

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
100 °C

Procedure

3-Ethynylphenol (187.0 mg, 103.7 μL, 1.583 mmol) was added to a solution of 3-bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine (500 mg, 1.319 mmol), Et3N (1.335 g, 1.839 mL, 13.19 mmol), Copper(I) iodide (30.15 mg, 0.1583 mmol) and Pd(PPh3)4 (76.21 mg, 0.06595 mmol) in DMF (5 mL) and the resulting solution heated at 100° C. for 90 minutes in a sealed tube. The reaction mixture was cooled to ambient temperature and diluted with EtOAc and 1MHCl/brine (1:1). The layers were separated and the aqueous layer was extracted with ethyl acetate (×2). The combined organics extracts were washed with brine, dried over (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 40 g column, eluting with 0 to 100% EtOAc/Petroleum Ether) to give the title product as a yellow solid (352 mg, 68% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, 6H), 3.44 (sept, 1H), 6.87-6.90 (m, 1H), 7.13-7.15 (m, 3H), 7.19-7.21 (m, 1H), 7.27 (t, 1H), 7.90 (d, J=8.6 Hz, 2H), 8.24 (d, J=8.6 Hz, 2H), 8.75 (s, 1H) and 9.77 (s, 1H) ppm; MS (ES+) 394.2.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (×2)
  4. washThe combined organics extracts were washed with brine
  5. dry with materialdried over (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ISCO Companion™, 40 g column, eluting with 0 to 100% EtOAc/Petroleum Ether)

Sources & evidence

ORD record
ord-d055277cf7eb442392078070f4c99a60
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

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