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

HRID 227519Notes

Reaction equation

HRID 227519 reaction equation
[CH3:1][S-:2].[Na+].Cl[C:5]1[C:10]([NH:11][C:12](=[O:23])[CH2:13][N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][OH:22])[CH2:16][CH2:15]2)=[C:9](Cl)[CH:8]=[C:7]([CH3:25])[N:6]=1.C1OCCOCCOCCOCCOCCOC1.C(Cl)(Cl)Cl.C[S:49]([CH3:51])=O>O>[OH:22][CH2:21][CH2:20][N:17]1[CH2:18][CH2:19][N:14]([CH2:13][C:12]([NH:11][C:10]2[C:5]([S:49][CH3:51])=[N:6][C:7]([CH3:25])=[CH:8][C:9]=2[S:2][CH3:1])=[O:23])[CH2:15][CH2:16]1

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 6212ChloroformHCID 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 62.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A 15% (w/v) aqueous solution (269 mL) of sodium thiomethoxide (576 mmol) was added to a solution of N-[2,4-dichloro-6-methylpyridin-3-yl]-2-[4-(2-hydroxyethyl)piperazin-1-yl]acetamide (10.0 g, 29 mmol) and 18-crown-6 (1.52 g, 5.8 mmol) in dimethyl sulfoxide (200 mL). The resulting mixture was stirred for 5 hours at 100° C. and further stirred for 1 hour at 110° C. The reaction mixture was allowed to cool, and chloroform and water were added thereto. The organic layer was collected, and the aqueous layer was further extracted with chloroform. The combined organic layer was washed sequentially with water and saturated brine, followed by drying over sodium sulfate anhydrate. The solvent was removed therefrom. The aqueous layer which had been employed for washing was extracted with chloroform, and the organic layer was washed sequentially with water and saturated brine. Subsequently, the solution was dried over sodium sulfate anhydrate, and the solvent was removed. The combined residue was purified through silica gel column chromatography (developer: chloroform/ammonia-saturated methanol=20/1), to thereby yield 6.63 g of 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide as colorless crystals (yield: 62.1%).

Workup

  1. stirringfurther stirred for 1 hour at 110° C
  2. temperatureto cool
  3. customThe organic layer was collected
  4. extractionthe aqueous layer was further extracted with chloroform
  5. washThe combined organic layer was washed sequentially with water and saturated brine
  6. dry with materialby drying over sodium sulfate anhydrate
  7. customThe solvent was removed
  8. washfor washing
  9. extractionwas extracted with chloroform
  10. washthe organic layer was washed sequentially with water and saturated brine
  11. dry with materialSubsequently, the solution was dried over sodium sulfate anhydrate
  12. customthe solvent was removed
  13. customThe combined residue was purified through silica gel column chromatography (developer: chloroform/ammonia-saturated methanol=20/1)

Sources & evidence

ORD record
ord-6e0f5ce62d01497bb500f47950b032e2
Source dataset
uspto-grants-2009_07
Patent number
US07560547B2

Reaction notes

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