Ethyl cyanoacetate → 1-Ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-2-benzimidazoleacetonitrile

HRID 1974628Notes

Reaction equation

HRID 1974628 reaction equation
[CH2:1]([NH:3][C:4]1[C:5]([N+:18]([O-])=O)=[CH:6][C:7]([F:17])=[C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)[CH:9]=1)[CH3:2].[C:21]([CH2:23][C:24](OCC)=O)#[N:22]>CO.[Pd]>[CH2:1]([N:3]1[C:4]2[CH:9]=[C:8]([N:10]3[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]3)[C:7]([F:17])=[CH:6][C:5]=2[N:18]=[C:24]1[CH2:23][C:21]#[N:22])[CH3:2]

Participants

5

Reactant 2

HCID 7764Ethyl cyanoacetateHCID 157514821-(5-(Ethylamino)-2-fluoro-4-nitrophenyl)-4-methylpiperazine

Product 1

HCID 191016981-Ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-2-benzimidazoleacetonitrileYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 23938PalladiumSolvent

Procedure

1-[5-(Ethylamino)-2-fluoro-4-nitrophenyl]-4-methylpiperazine (2.8 g, 10 mmol) is dissolved in methanol (200 ml) and hydrogenated with 5 percent palladium/carbon under hydrogen at normal pressure. The palladium/carbon is filtered off and the filtrate is evaporated under reduced pressure. The residue is dried in a high vacuum, dissolved in diethyl glycol ethyl ether (10 ml) and then treated with ethyl cyanoacetate (2.26 g, 20 mmol). The solution is heated to 160° for 4 hours. The solvent is then distilled off and the residue is taken up in an acetic acid/ether mixture (100 ml, 1:2). The crystals obtained are filtered off, dissolved in an ethyl acetate/methanol mixture (6:4 and chromatographed on silica gel (eluent: ethyl acetate/methanol 6:4). The product is recrystallized from an ethyl acetate/acetonitrile mixture (9:1). There are obtained 1.17 g (39%) of 1-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-2-benzimidazoleacetonitrile with a m.p. of 204°-206°.

Workup

  1. filtrationThe palladium/carbon is filtered off
  2. customthe filtrate is evaporated under reduced pressure
  3. customThe residue is dried in a high vacuum
  4. dissolutiondissolved in diethyl glycol ethyl ether (10 ml)
  5. temperatureThe solution is heated to 160° for 4 hours
  6. distillationThe solvent is then distilled off
  7. customThe crystals obtained
  8. filtrationare filtered off
  9. dissolutiondissolved in an ethyl acetate/methanol mixture (6:4
  10. customchromatographed on silica gel (eluent: ethyl acetate/methanol 6:4)
  11. customThe product is recrystallized from an ethyl acetate/acetonitrile mixture (9:1)

Sources & evidence

ORD record
ord-686905271da4429ea04339d36f4c034e
Source dataset
uspto-grants-1994_02
Patent number
US05283248

Reaction notes

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