Sodium Cyanide → 2-{3-[4-(2-hydroxyphenyl)-piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide

HRID 2294151Notes

Reaction equation

HRID 2294151 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]2[N:29]=[CH:28][CH:27]=[CH:26][C:20]=2[C:21]([N:23]([CH3:25])[CH3:24])=[O:22])[CH2:11][CH2:10]1.[C-]#N.[Na+]>CS(C)=O.O>[OH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]2[N:29]=[CH:28][CH:27]=[CH:26][C:20]=2[C:21]([N:23]([CH3:25])[CH3:24])=[O:22])[CH2:13][CH2:14]1

Participants

5

Reactant 2

HCID 8929Sodium CyanideHCID 98655772-(3-(4-(2-Methoxyphenyl)piperazin-1-yl)propylamino)-N,N-dimethylnicotinamide

Product 1

HCID 106436992-{3-[4-(2-hydroxyphenyl)-piperazin-1-yl]propylamino}-N,N-dimethylnicotinamideYield 25.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A mixture of 2-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide (0.54 g, 1.36 mmol), prepared as in Example 21, and sodium cyanide (0.33 g, 6.8 mmol) in 12 mL of DMSO was heated at reflux for 14 hours and then diluted with water and extracted twice with diethyl ether. The aqueous layer was extracted twice with methylene chloride and the combined methylene chloride layers were washed with water and brine, dried (MgSO4), filtered and concentrated. The residue was purified on silica gel by column chromatography eluting with 8% methanol/methylene chloride to give 2-{3-[4-(2-hydroxyphenyl)-piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide (0.134 g, 0.35 mmol) as an oil. The free base was recrystallized from a solution of fumaric acid in alcohol to give di(2-{3-[4-(2-hydroxyphenyl)-piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide) fumarate, m.p. 185°-186° C. Anal.: Calcd. for C21H30N5O2.(C4H4O4)0.5 : C, 62.57; H, 7.08; N, 15.86; Found: C, 62.44H, 7.08; N, 15.73%.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 14 hours
  3. extractionextracted twice with diethyl ether
  4. extractionThe aqueous layer was extracted twice with methylene chloride
  5. washthe combined methylene chloride layers were washed with water and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified on silica gel by column chromatography
  10. washeluting with 8% methanol/methylene chloride

Sources & evidence

ORD record
ord-7444e28842e546908b42646dfb0a8d63
Source dataset
uspto-grants-1997_11
Patent number
US05688795

Reaction notes

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