Hydrochloric Acid → 3-[3-(N-benzyl-N-methylamino)-propyloxy]-2-methyl-5-(2-fluorophenyl)-pyrazole

HRID 1489645Notes

Reaction equation

HRID 1489645 reaction equation
[CH3:1][N:2]1[C:6](=[O:7])[CH2:5][CH:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])[NH:3]1.[H-].[Na+].[CH2:17]([N:24]([CH2:26][CH2:27][CH2:28]Cl)[CH3:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>CN1CCCN(C)C1=O.C(O)(C)C.COC(C)(C)C.CC(C)=O>[CH2:17]([N:24]([CH2:26][CH2:27][CH2:28][O:7][C:6]1[N:2]([CH3:1])[N:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])[CH:5]=1)[CH3:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 22067N-benzyl-3-chloro-N-methylpropan-1-amineHCID 24758Sodium hydrideHCID 229023552-Methyl-5-(2-fluorophenyl)-pyrazolin-3-one

Product 1

HCID 229023893-[3-(N-benzyl-N-methylamino)-propyloxy]-2-methyl-5-(2-fluorophenyl)-pyrazoleYield 74.6%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 3776IsopropanolSolventHCID 15413tert-Butyl methyl etherSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
80 °C

Procedure

3.3 g of 2-methyl-5-(2-fluorophenyl)-pyrazolin-3-one were dissolved in 50 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone. 0.55 g of sodium hydride (as an 80 % strength solution in paraffin) was added to this solution and the reaction mixture was stirred at 80° C. for 30 minutes. 3.3 g of 3-(N-benzyl-N-methylamino)-propyl chloride were added to the reaction mixture which was stirred at 80° C. for a further 2 hours. After the reaction mixture had cooled, 10 ml of a 2N solution of hydrochloric acid in isopropanol were added to it, and the mixture was then added dropwise to 2 liters of a 1:3 mixture of acetone and tert-butyl methyl ether. The resulting precipitate was filtered out and dissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate. The organic phase was separated and the aqueous phase was subsequently extracted repeatedly with ethyl acetate. The combined ethyl acetate extracts were dried with sodium sulfate and evaporated. The crude base obtained was purified by chromatography on silica gel. 4.4 g of 3-[3-(N-benzyl-N-methylamino)-propyloxy]-2-methyl-5-(2-fluorophenyl)-pyrazole were obtained.

Workup

  1. stirringwas stirred at 80° C. for a further 2 hours
  2. temperatureAfter the reaction mixture had cooled
  3. filtrationThe resulting precipitate was filtered out
  4. dissolutiondissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was subsequently extracted repeatedly with ethyl acetate
  7. dry with materialThe combined ethyl acetate extracts were dried with sodium sulfate
  8. customevaporated
  9. customThe crude base obtained
  10. customwas purified by chromatography on silica gel

Sources & evidence

ORD record
ord-7e3de3666dd54c8cb27a276904e7df79
Source dataset
uspto-grants-1997_10
Patent number
US05679699

Reaction notes

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