Triethylamine → 2-Bromo-N-(6-methyl-2,4-bis(methylthio)pyridin-3-yl)acetamide

HRID 2103967Notes

Reaction equation

HRID 2103967 reaction equation
CS(Cl)(=O)=O.[CH3:6][S:7][C:8]1[C:13]([NH:14][C:15](=[O:18])[CH2:16]O)=[C:12]([S:19][CH3:20])[CH:11]=[C:10]([CH3:21])[N:9]=1.C(N(CC)CC)C.[Br-:29].[Na+]>CN(C)C1C=CN=CC=1.CN(C=O)C.O>[CH3:6][S:7][C:8]1[C:13]([NH:14][C:15](=[O:18])[CH2:16][Br:29])=[C:12]([S:19][CH3:20])[CH:11]=[C:10]([CH3:21])[N:9]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 253881Sodium BromideHCID 69064831HCID 69064831, compound

Product 1

HCID 222471492-Bromo-N-(6-methyl-2,4-bis(methylthio)pyridin-3-yl)acetamideYield 67.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
11 °C

Procedure

Under cooling with ice, methanesulfonyl chloride (31.7 g, 276.7 mmol) was added dropwise to a solution of N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-hydroxyacetamide (65.0 g, 251.6 mmol), triethylamine (30.5 g, 301.4 mmol), and 4-dimethylaminopyridine (3.07 g, 25.13 mmol) in DMF (455 mL) while the reaction mixture was maintained at 11° C. or lower, followed by stirring for 0.5 hours under cooling with ice. After HPLC was performed to confirm that starting materials had been completely consumed, the crystals (triethylamine hydrochloride) that precipitated were collected through filtration, followed by washing with DMF (195 mL). The filtrate and the wash liquid were combined, and sodium bromide (51.8 g, 503.5 mmol) was added to the resultant mixture. The reaction mixture was stirred under heat at an internal temperature of 55 to 60° C. for 3 hours. Subsequently, water (650 mL) was added to the reaction mixture, and the resultant mixture was stirred at an internal temperature of 21 to 25° C. for 2 hours. The crystals that precipitated were collected through filtration, followed by washing with water and drying through air blow. The crude target product was dissolved in methanol (500 mL) through heating, and the reaction mixture was cooled. The crystals that precipitated were collected through filtration, followed by drying through air blow at 60° C., to thereby yield N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-bromoacetamide (54.38 g, yield: 67.3%, HPLC: 99.32%).

Workup

  1. temperatureunder cooling with ice
  2. customhad been completely consumed
  3. customthe crystals (triethylamine hydrochloride) that precipitated
  4. filtrationwere collected through filtration
  5. washby washing with DMF (195 mL)
  6. stirringThe reaction mixture was stirred
  7. temperatureunder heat at an internal temperature of 55 to 60° C. for 3 hours
  8. customThe crystals that precipitated
  9. filtrationwere collected through filtration
  10. washby washing with water
  11. customdrying through air blow
  12. dissolutionThe crude target product was dissolved in methanol (500 mL)
  13. temperaturethrough heating
  14. temperaturethe reaction mixture was cooled
  15. customThe crystals that precipitated
  16. filtrationwere collected through filtration
  17. customby drying through air blow at 60° C.

Sources & evidence

ORD record
ord-19ca3971f6984db0bf7cde7398e7f26f
Source dataset
uspto-grants-2009_08
Patent number
US07576203B2

Reaction notes

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