1-Methylpiperazine → 3-methoxy-4-nitro-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-ylcarbonyl)pent-1-yloxy]phenyl]benzamide

HRID 1005580Notes

Reaction equation

HRID 1005580 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][C:28]=1[N+:29]([O-:31])=[O:30])[C:6]([N:8]([C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:11]=1[O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=O)[CH3:9])=[O:7].[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(OCC)(=O)C.C(Cl)(Cl)Cl.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][C:28]=1[N+:29]([O-:31])=[O:30])[C:6]([N:8]([CH3:9])[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:11]=1[O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([N:36]1[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]1)=[O:25])=[O:7]

Participants

9

Reactant 4

HCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 187914763-methoxy-4-nitro-N-[2-(5-carboxypent-1-yloxy)-4-methylphenyl]-N-methylbenzamide

Product 1

HCID 187914403-methoxy-4-nitro-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-ylcarbonyl)pent-1-yloxy]phenyl]benzamideYield 100.1%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Methoxy-4-nitro-N-[2-(5-carboxypent-1-yloxy)-4-methylphenyl]-N-methylbenzamide (5.2 g), 1-methylpiperazine (1.45 g) and 1-hydroxybenzotriazole (1.96 g) were dissolved in N,N-dimethylformamide (50 ml) and the solution was cooled in an ice bath. To the mixture was added N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (2.78 g) and the solution was stirred at the same temperature for 30 minutes. The reaction mixture was allowed to warm to ambient temperature and stirring was continued for additional 20 hours. The reaction mixture was diluted with ethyl acetate and the solution was washed successively with saturated sodium hydrogen carbonate and brine, and dried over sodium sulfate. The sodium sulfate was removed and the solvent was removed by evaporation to give oil. The crude material was subjected to a silica gel column chromatography (SiO2 ; 120 g, 2% methanol in chloroform) to give 3-methoxy-4-nitro-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-ylcarbonyl)pent-1-yloxy]phenyl]benzamide (6.2 g).

Workup

  1. temperaturethe solution was cooled in an ice bath
  2. stirringstirring
  3. waitwas continued for additional 20 hours
  4. washthe solution was washed successively with saturated sodium hydrogen carbonate and brine
  5. dry with materialdried over sodium sulfate
  6. customThe sodium sulfate was removed
  7. customthe solvent was removed by evaporation
  8. customto give oil

Sources & evidence

ORD record
ord-d2b6340a79fd4946a41edc84ef607bb9
Source dataset
uspto-grants-2000_04
Patent number
US06054457

Reaction notes

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