2,2',4'-Trichloroacetophenone → Piperazine, 1-[(2,4-dichlorobenzoyl)methyl]-4-methyl-

HRID 31782Notes

Reaction equation

HRID 31782 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:12])[CH2:10]Cl.[CH3:13][N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:12])[CH2:10][N:17]1[CH2:18][CH2:19][N:14]([CH3:13])[CH2:15][CH2:16]1

Participants

4

Reactant 2

HCID 202502,2',4'-TrichloroacetophenoneHCID 531671-Methylpiperazine

Product 1

HCID 551008Piperazine, 1-[(2,4-dichlorobenzoyl)methyl]-4-methyl-

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(2,4-dichlorophenyl)-2-chloroethan-1-one(1 mmol) and methylpiperazine (4 mmol) in 8 ml DMF was stirred for 8 h at room temperature. The reaction mixture was concentrated in vacuo and extracted into ethyl acetate and the organic layer was washed with water and dried with sodium sulfate. The residue after concentration in vacuo was purified by column chromatography eluting with 10% methanol in methylene chloride to yield 1-(2,4-dichlorophenyl)-2-(4-methylpiperazinyl)ethan-1-one. The ethanone was taken up in DMF-DMA and heated to 80° C. for 6 h. The reaction mixture was cooled and concentrated in vacuo and the residue containing the enaminone was purified by column chromatography. 1 mmol of the enaminone obtained above, 1 mmol of amino {2-[(6-amino-5-nitro(2-pyridyl))amino]ethyl}carboxamidine hydrochloride and 3 mmol of Cs2CO3 was suspended in DMF and heated to 90° C. for fourteen hours. The reaction was cooled and concentrated in vacuo. The residue was partitioned between water and ethyl acetate and the layers separated. The organic layers were dried with sodium sulfate and after solvent removal were chromatographed on silica gel eluting with 5-10% methanol in methylene chloride to obtain {2-[(6-amino-5-nitro(2-pyridyl))amino]ethyl}[4-(2,4-dichlorophenyl)-5-(4-methylpiperazinyl)pyrimidin-2-yl]amine as a yellow powder after lyophilization.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. extractionextracted into ethyl acetate
  3. washthe organic layer was washed with water
  4. dry with materialdried with sodium sulfate
  5. concentrationThe residue after concentration in vacuo
  6. customwas purified by column chromatography
  7. washeluting with 10% methanol in methylene chloride

Sources & evidence

ORD record
ord-c2266ce75fcb4ba0ab84a9a6050ca287
Source dataset
uspto-grants-2008_09
Patent number
US07425557B2

Reaction notes

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