Sodium Carbonate → 2-Chloro-6-(4-(isopropylsulfonyl)phenyl)pyrazine

HRID 522529Notes

Reaction equation

HRID 522529 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[CH:9]([S:12]([C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1)(=[O:14])=[O:13])([CH3:11])[CH3:10].C([O-])([O-])=O.[Na+].[Na+]>C(O)C.C1(C)C=CC=CC=1.O.C(Cl)Cl.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>[Cl:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:18]2[CH:17]=[CH:16][C:15]([S:12]([CH:9]([CH3:11])[CH3:10])(=[O:14])=[O:13])=[CH:20][CH:19]=2)[N:3]=1

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 785042,6-DichloropyrazineHCID 441193274-(Isopropylsulphonyl)benzeneboronic acid

Product 1

HCID 866651482-Chloro-6-(4-(isopropylsulfonyl)phenyl)pyrazineYield 49.3%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2,6-dichloropyrazine (653.1 mg, 4.384 mmol), (4-isopropylsulfonylphenyl)boronic acid (500 mg, 2.192 mmol), Pd(PPh3)4 (126.6 mg, 0.1096 mmol) and Na2CO3 (2.192 mL of 2 M, 4.384 mmol) in ethanol (500.0 μL) and toluene (7.500 mL) was heated at reflux for 72 hours. The reaction mixture was cooled to ambient temperature and diluted with water and DCM. The layers were separated and the aqueous layer was extracted with DCM (×3). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 40 g column, eluting with 0 to 40% EtOAc/Petroleum Ether) to give the sub-title product as a white solid (321 mg, 49% Yield). 1H NMR (400.0 MHz, DMSO) δ 9.41 (s, 1H), 8.88 (s, 1H), 8.41 (d, 2H), 8.03 (d, 2H), 3.54-3.49 (m, 1H) and 1.19 (d, 6H) ppm; MS (ES+) 297.1

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 72 hours
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (×3)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ISCO Companion™, 40 g column, eluting with 0 to 40% EtOAc/Petroleum Ether)

Sources & evidence

ORD record
ord-3e0a94bf71794b098dd665f69c5775c6
Source dataset
uspto-grants-2016_05
Patent number
US09334244B2

Reaction notes

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