Dimethyl Sulfoxide → 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide

HRID 227542Notes

Reaction equation

HRID 227542 reaction equation
Cl[C:2]1[C:7]([NH:8][C:9](=[O:20])[CH2:10][N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][OH:19])[CH2:13][CH2:12]2)=[C:6](Cl)[CH:5]=[C:4]([CH3:22])[N:3]=1.C1OCCOCCOCCOCCOCCOC1.[CH3:41][S-:42].[Na+].O.C[S:46]([CH3:48])=O>>[OH:19][CH2:18][CH2:17][N:14]1[CH2:15][CH2:16][N:11]([CH2:10][C:9]([NH:8][C:7]2[C:2]([S:46][CH3:48])=[N:3][C:4]([CH3:22])=[CH:5][C:6]=2[S:42][CH3:41])=[O:20])[CH2:12][CH2:13]1

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 2855718-Crown-6HCID 4378561Sodium methanethiolateHCID 10020570N-(2,4-dichloro-6-methylpyridin-3-yl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]acetamide

Product 1

HCID 116892402-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamideYield 71%

Procedure

N-(2,4-Dichloro-6-methylpyridin-3-yl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]acetamide (58.0 g, 167.0 mmol) and 18-crown-6 (4.41 g, 16.7 mmol) were dissolved in dimethyl sulfoxide (580 mL), and sodium thiomethoxide powder (46.8 g, 667.7 mmol) was added to the solution under stirring and under cooling with ice, followed by stirring for 2.5 hours at an inner temperature of 65-75° C. The reaction mixture was allowed to cool to room temperature, and water was added to the mixture under cooling with ice, followed by extraction with chloroform. The aqueous layer was extracted with chloroform. The combined organic layer was washed with saturated brine and concentrated under reduced pressure. The residue was recrystallized from isopropanol and diisopropyl ether, to thereby yield 43.83 g of 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide (yield: 71%) as colorless crystals.

Workup

  1. temperatureunder cooling with ice
  2. stirringby stirring for 2.5 hours at an inner temperature of 65-75° C
  3. temperatureunder cooling with ice
  4. extractionfollowed by extraction with chloroform
  5. extractionThe aqueous layer was extracted with chloroform
  6. washThe combined organic layer was washed with saturated brine
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was recrystallized from isopropanol and diisopropyl ether

Sources & evidence

ORD record
ord-5a02837d5c5c4f0dbff3aec076ef21e1
Source dataset
uspto-grants-2009_07
Patent number
US07560547B2

Reaction notes

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