Hydrochloric Acid → 3-Pyridinamine, N-methyl-4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)-

HRID 379419Notes

Reaction equation

HRID 379419 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[CH:12][C:11]([NH2:14])=[C:10]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH3:21])[CH:9]=2)[CH2:4][CH2:3]1.[Li].Cl.[OH-].[Na+].[CH3:26]OC(OC)OC>FC(F)(F)C(O)=O.O1CCCC1>[CH3:26][NH:14][C:11]1[CH:12]=[N:13][C:8]([N:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)=[CH:9][C:10]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH3:21]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9005Trimethyl orthoformateHCID 14798Sodium HydroxideHCID 3028194LithiumHCID 158874116-(4-Methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-amine

Product 1

HCID 158874123-Pyridinamine, N-methyl-4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)-Yield 64%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

35 g (124 mMol) 6-(4-Methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-ylamine were dissolved in 273 ml ortho-formic acid trimethyl ester and 8 drops trifluoroacetic acid were added. The reaction mixture was refluxed for 3 hours then concentrated under reduced pressure and dried under high vacuum. The residue was dissolved in 100 ml tetrahydrofuran and added dropwise at 0° C. to a suspension of 9.4 g (248 mMol) lithium alimunium hydride in 300 ml tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 hour, cooled again to 0° C. and its pH was brought to 1 by careful addition of aqueous HCl 28%. After 5 minutes, the pH was raised to 10 by addition of aqueous NaOH 28%, the reaction mixture was filtered on Hyflo and concentrated under reduced pressure. The residue was chromatographed (eluent: dichloromethane/methanol 9:1) to yield 23.6 g (64%) methyl-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-amine as a brown oil.

Workup

  1. temperatureThe reaction mixture was refluxed for 3 hours
  2. concentrationthen concentrated under reduced pressure
  3. customdried under high vacuum
  4. dissolutionThe residue was dissolved in 100 ml tetrahydrofuran
  5. temperaturecooled again to 0° C.
  6. waitAfter 5 minutes
  7. filtrationthe reaction mixture was filtered on Hyflo
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was chromatographed (eluent: dichloromethane/methanol 9:1)

Sources & evidence

ORD record
ord-7e58db6ea8fe4ec19913198af3125322
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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