Hydrochloric Acid → K-604

HRID 2103966Notes

Reaction equation

HRID 2103966 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:15][S:16][C:17]1[C:22]([NH:23][C:24](=[O:27])[CH2:25]O)=[C:21]([S:28][CH3:29])[CH:20]=[C:19]([CH3:30])[N:18]=1.I(O)(=O)=O.[N:35]1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[NH:37][C:36]=1[S:44][CH2:45][CH2:46][N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>CN(C)C=O.C(OCC)(=O)C.O>[N:35]1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[NH:37][C:36]=1[S:44][CH2:45][CH2:46][N:47]1[CH2:52][CH2:51][N:50]([CH2:25][C:24]([NH:23][C:22]2[C:17]([S:16][CH3:15])=[N:18][C:19]([CH3:30])=[CH:20][C:21]=2[S:28][CH3:29])=[O:27])[CH2:49][CH2:48]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 69064831N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-hydroxyacetamideHCID 866186761-[2-(Benzimidazol-2-ylthio)ethyl]piperazine iodate

Product 1

HCID 9892288K-604Yield 94%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diisopropyl azodicarboxylate (0.770 mL, 1.52 mmol) was added dropwise to a solution of N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-hydroxyacetamide (131 mg, 0.508 mmol), 1-[2-(benzimidazol-2-ylthio)ethyl]piperazine iodate (933 mg, 1.88 mmol) and triphenylphosphine (470 mg, 1.79 mmol) in dimethylformamide (3 mL) under stirring with water cooling over 5 minutes. The resultant mixture was stirred at room temperature for 60 minutes, and water (10 mL) was added thereto. Subsequently, 1 mol/L hydrochloric acid (10 mL) and ethyl acetate (30 mL) were added the reaction mixture, to thereby collect the aqueous layer. The organic layer was extracted with 1 mol/L hydrochloric acid (10 mL×2). The obtained aqueous layers were combined, and the thus-combined aqueous layer was washed with ethyl acetate (30 mL×2). The pH of the resultant mixture was adjusted to 8 to 9 with a 1 mol/L aqueous sodium hydroxide solution, followed by extraction with ethyl acetate (30 mL×3). The organic layers were combined, and the thus-combined organic layer was washed with saturated brine. The thus-washed organic layer was dried over sodium sulfate anhydrate, and the solvent was removed under reduced pressure. The crude product was purified through silica gel column chromatography (silica gel: 40 g, developer: chloroform:methanol=100:3), to thereby yield 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide (240 mg, yield: 94%).

Workup

  1. customto thereby collect the aqueous layer
  2. extractionThe organic layer was extracted with 1 mol/L hydrochloric acid (10 mL×2)
  3. washthe thus-combined aqueous layer was washed with ethyl acetate (30 mL×2)
  4. extractionfollowed by extraction with ethyl acetate (30 mL×3)
  5. washthe thus-combined organic layer was washed with saturated brine
  6. dry with materialThe thus-washed organic layer was dried over sodium sulfate anhydrate
  7. customthe solvent was removed under reduced pressure
  8. customThe crude product was purified through silica gel column chromatography (silica gel: 40 g, developer: chloroform:methanol=100:3)

Sources & evidence

ORD record
ord-61526dc6aec740468d71a44795603031
Source dataset
uspto-grants-2009_08
Patent number
US07576203B2

Reaction notes

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