2,3-Dichloroquinoxaline → 2-Chloro-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxaline

HRID 1621651Notes

Reaction equation

HRID 1621651 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([S:8][CH3:9])[CH:5]=[C:4]([Sn](CCCC)(CCCC)CCCC)[N:3]=1.[Cl:23][C:24]1[C:33](Cl)=[N:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=1>C1(C)C=CC=CC=1.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:23][C:24]1[C:33]([C:4]2[CH:5]=[C:6]([S:8][CH3:9])[N:7]=[C:2]([CH3:1])[N:3]=2)=[N:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=1

Participants

5

Reactant 2

HCID 166592,3-DichloroquinoxalineHCID 595482802-Methyl-4-(methylthio)-6-(tributylstannyl)pyrimidine

Product 1

HCID 866470562-Chloro-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxalineYield 70.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with 2-methyl-4-(methylthio)-6-(tributylstannyl)pyrimidine (1.6 g, 3.73 mmol), 2,3-dichloroquinoxaline (1.484 g, 7.45 mmol, Aldrich) and tetrakis(triphenylphosphine)palladium (0.431 g, 0.373 mmol, Strem Chemicals) in toluene (5 mL). Argon was bubbled through for 2 min. The reaction mixture was stirred and heated at 120° C. for 36 h. The mixture was cooled to room temperature, filtered through Celite® (diatomaceous earth) washing with 10% methanol-DCM, and the filtrate was concentrated. The crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0-100% DCM-hexane to give 2-chloro-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxaline (0.8 g, 2.64 mmol, 70.9% yield) as a white solid. 1H NMR (400 MHz, d6-DMSO) δ 8.23 (dd, J=8.02, 1.56 Hz, 1H); 8.13-8.19 (m, 1H); 7.96-8.05 (m, 2H); 7.73 (s, 1H); 2.67 (s, 3H); 2.61 (s, 3H). m/z (ESI, +ve ion) 303 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. customArgon was bubbled through for 2 min
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through Celite® (diatomaceous earth)
  5. washwashing with 10% methanol-DCM
  6. concentrationthe filtrate was concentrated
  7. customThe crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 0-100% DCM-hexane

Sources & evidence

ORD record
ord-10b5dc4896034b50bf4e2177547eeb58
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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