1-Methylpiperazine → 4-[2-(3,5-Dichloro-4-pyridyl)-1-oxoethyl]-2-(4-methyl-1-piperazinyl)carbonyl-7-methoxybenzofuran

HRID 1937417Notes

Reaction equation

HRID 1937417 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[CH2:8][C:9]([C:11]1[C:16]2[CH:17]=[C:18]([C:20]([OH:22])=O)[O:19][C:15]=2[C:14]([O:23][CH3:24])=[CH:13][CH:12]=1)=[O:10].O.ON1C2C=CC=CC=2N=N1.[CH3:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[CH2:8][C:9]([C:11]1[C:16]2[CH:17]=[C:18]([C:20]([N:41]3[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]3)=[O:22])[O:19][C:15]=2[C:14]([O:23][CH3:24])=[CH:13][CH:12]=1)=[O:10]

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 27960291-Hydroxybenzotriazole hydrateHCID 227341684-[2-(3,5-Dichloro-4-pyridyl)-1-oxoethyl]-7-methoxybenzofuran-2-carboxylic acid2×

Product 1

HCID 154632804-[2-(3,5-Dichloro-4-pyridyl)-1-oxoethyl]-2-(4-methyl-1-piperazinyl)carbonyl-7-methoxybenzofuranYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[2-(3,5-Dichloro-4-pyridyl)-1-oxoethyl]-7-methoxybenzofuran-2-carboxylic acid (Compound M, 5.8 g) obtained in Reference Example 3 was dissolved in DMF (700 ml), and 1-hydroxybenzotriazole monohydrate (8.4 g), N-ethyl-N′-3-dimethylaminopropylcarbodiimide monohydrochloride (11.6 g) and 1-methylpiperazine (6.8 ml) were added thereto, and the mixture was stirred at room temperature for 5 hours. After the solvent was distilled off under reduced pressure, the residue was extracted with chloroform, washed with a saturated aqueous sodium chloride solution, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol 80:1 to 20:1) and then recrystallized from ethanol to give Compound 13 (5.5 g, 79%) as colorless crystals.

Workup

  1. distillationAfter the solvent was distilled off under reduced pressure
  2. extractionthe residue was extracted with chloroform
  3. washwashed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified by silica gel column chromatography (chloroform:methanol 80:1 to 20:1)
  7. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-d1aec408e6894deba5f5e55901a385b2
Source dataset
uspto-grants-2002_05
Patent number
US06395738B1

Reaction notes

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