Benzyl Chloride → HCID 13849866, compound

HRID 414467Notes

Reaction equation

HRID 414467 reaction equation
[Cl:1]CCN[C:5]1[CH:10]=[C:9]([CH3:11])N=[C:7]([CH3:12])[C:6]=1[N+]([O-])=O.C(N1CCNCC1)=O.C(N(CC)CC)C.[CH3:31][C:32]1[C:37]([N+:38]([O-:40])=[O:39])=[C:36]([NH:41][CH2:42][CH2:43][N:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)[CH:35]=[C:34]([CH3:50])[N:33]=1.C([Cl:58])C1C=CC=CC=1>C(O)(C)C>[ClH:1].[ClH:58].[ClH:1].[CH2:12]([N:47]1[CH2:46][CH2:45][N:44]([CH2:43][CH2:42][NH:41][C:36]2[CH:35]=[C:34]([CH3:50])[N:33]=[C:32]([CH3:31])[C:37]=2[N+:38]([O-:40])=[O:39])[CH2:49][CH2:48]1)[C:7]1[CH:6]=[CH:5][CH:10]=[CH:9][CH:11]=1

Participants

7

Reactant 5

HCID 7503Benzyl ChlorideHCID 8471Triethylamine2×HCID 821911-PiperazinecarboxaldehydeHCID 14448154HCID 14448154, compoundHCID 21280926HCID 21280926, compound

Product 1

HCID 13849866HCID 13849866, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

13.3 g (0.05 mol) of 4-(2-chloroethylamino)-2,6-dimethyl-3-nitropyridine, 8.56 g (0.075 mole) of 1-formylpiperazine and 10 g (0.1 mol) of triethylamine were heated to boiling in 300 ml of isopropanol for 10 hours. The liquids were removed by distillation in vacuo, and the remaining solid residue was partitioned between dichloromethane an water by shaking. The dichloromethane phase was evaporated, and the residue was recrystallized once from isopropanol and heated to boiling in 6N hydrochloric acid for 2 hours. The solution was then adjusted to pH 7 with 10% strength sodium hydroxide solution, and the water was removed by distillation. The solid residue was purified on silica gel using dichloromethane/methanol (8:2; vol). 4.5 g (0.016 mol) [31.8% of theory] of 2,6-dimethyl-3-nitro-4-[(2-(1-piperazinyl)ethyl)amino]pyridine (melting point of the trihydrochloride 128°-129° C.) were obtained and were heated to reflux with 2.15 g (0.017 mol) of benzyl chloride and 2 g (0.02 mol) of triethylamine in 100 ml of isopropanol for 6 hours in accordance with process variant (b). The solvents were removed by distillation, and the oily residue was extracted by stirring with ethyl acetate, and the mixture was filtered and the filtrate was evaporated to dryness. The residue was taken up in ethanol, ethanolic HCl was added, nd the mixture was evaporated to dryness. The residue from evaporation was recrystallized from isopropanol/diisopropyl ether (4:1; vol.).

Workup

  1. customThe liquids were removed by distillation in vacuo
  2. customthe remaining solid residue was partitioned between dichloromethane an water
  3. customThe dichloromethane phase was evaporated
  4. customthe residue was recrystallized once from isopropanol
  5. temperatureheated
  6. customthe water was removed by distillation
  7. customThe solid residue was purified on silica gel
  8. customwere obtained
  9. temperaturewere heated
  10. customThe solvents were removed by distillation
  11. extractionthe oily residue was extracted
  12. stirringby stirring with ethyl acetate
  13. filtrationthe mixture was filtered
  14. customthe filtrate was evaporated to dryness
  15. additionethanolic HCl was added
  16. customnd the mixture was evaporated to dryness
  17. customThe residue from evaporation
  18. customwas recrystallized from isopropanol/diisopropyl ether (4:1; vol.)

Sources & evidence

ORD record
ord-e14ac34a13e34d0fa54a9f49a65b618a
Source dataset
uspto-grants-1988_12
Patent number
US04792554

Reaction notes

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