Triethylamine → K-604

HRID 227521Notes

Reaction equation

HRID 227521 reaction equation
O[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]([NH:13][C:14]2[C:15]([S:23][CH3:24])=[N:16][C:17]([CH3:22])=[CH:18][C:19]=2[S:20][CH3:21])=[O:12])[CH2:6][CH2:5]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[SH:37][C:38]1[NH:39][C:40]2[CH:46]=[CH:45][CH:44]=[CH:43][C:41]=2[N:42]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>O1CCCC1.CN(C)C1C=CN=CC=1>[N:39]1[C:40]2[CH:46]=[CH:45][CH:44]=[CH:43][C:41]=2[NH:42][C:38]=1[S:37][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]([NH:13][C:14]2[C:15]([S:23][CH3:24])=[N:16][C:17]([CH3:22])=[CH:18][C:19]=2[S:20][CH3:21])=[O:12])[CH2:6][CH2:5]1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 31297Methanesulfonyl chlorideHCID 116892402-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamideHCID 178527775HCID 178527775, compound

Product 1

HCID 9892288K-604Yield 39.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

2-[4-(2-Hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide (104.94 g, 0.286 mol) was dissolved in tetrahydrofuran (1.4 L), and triethylamine (48.5 g, 0.479 mol), 4-dimethylaminopyridine (1.76 g, 14.4 mmol), and methanesulfonyl chloride (42 g, 0.366 mol) were sequentially added to the solution under cooling with ice, followed by stirring for 1 hour at the same temperature. The reaction mixture was filtrated, and the filtrate was concentrated under reduced pressure, to thereby yield 144.92 g of a pale yellow foamed substance. The product was dissolved in N,N-dimethylformamide (1 L), and 2-mercaptobenzimidazole (48.58 g, 0.323 mol), potassium carbonate (48.58 g, 0.351 mol), and 18-crown-6 (3.56 g, 13.5 mmol) were added to the resultant solution at room temperature, followed by stirring for 3 hours at 80° C. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding chloroforn and water. The aqueous layer was extracted with chloroform. The combined organic layer was washed with saturated brine, dried over sodium sulfate anhydrate, and concentrated under reduced pressure. The residue was purified through silica gel column chromatography (developer: hexane/acetone=1/1-1/3), to thereby yield 55.85 g of 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide (yield: 39.2%).

Workup

  1. temperatureunder cooling with ice
  2. filtrationThe reaction mixture was filtrated
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe product was dissolved in N,N-dimethylformamide (1 L)
  5. stirringby stirring for 3 hours at 80° C
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. customthe residue was partitioned
  8. additionby adding chloroforn and water
  9. extractionThe aqueous layer was extracted with chloroform
  10. washThe combined organic layer was washed with saturated brine
  11. dry with materialdried over sodium sulfate anhydrate
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified through silica gel column chromatography (developer: hexane/acetone=1/1-1/3)

Sources & evidence

ORD record
ord-f19278511a9549238ed90758a62b2a8b
Source dataset
uspto-grants-2009_07
Patent number
US07560547B2

Reaction notes

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