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

HRID 227518Notes

Reaction equation

HRID 227518 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 Sulfoxide2×HCID 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 90.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A solution of sodium thiomethoxide (7.0 g, 100 mmol) in dimethyl sulfoxide (100 mL) was added to a solution of N-[2,4-dichloro-6-methylpyridin-3-yl]-2-[4-(2-hydroxyethyl)piperazin-1-yl]acetamide (7.0 g, 20 mmol) and 18-crown-6 (530 mg, 2 mmol) in dimethyl sulfoxide (14 mL). The resulting mixture was stirred for 1 hour at 100° C. The reaction mixture was allowed to cool, and then chloroform and water were added thereto. The organic layer was collected from the mixture, and the aqueous layer was firther extracted with chloroform. The organic layers were combined together, and 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 obtained 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 6.68 g of 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide as colorless crystals (yield: 90.1%). The product was recrystallized from ethanol-diethyl ether, to thereby yield the product as colorless needles.

Workup

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

Sources & evidence

ORD record
ord-0dc568949a6a4c62b83417e86bc2a206
Source dataset
uspto-grants-2009_07
Patent number
US07560547B2

Reaction notes

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