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

HRID 379376Notes

Reaction equation

HRID 379376 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.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.[OH-].[Na+].[CH:31](OC)(OC)OC>FC(F)(F)C(O)=O.O1CCCC1>[CH3:31][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 158874116-(4-Methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-amineHCID 21226445Aluminium lithium hydride

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

A solution of 35 g (124 mmol) 6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-ylamine in 270 ml trimethyl orthoformate and 8 drops trifluoroacetic acid was heated for 3 h at 130° C. The reaction mixture was evaporated and dried in vacuo for 30 min. The residual oil was dissolved in 100 ml tetrahydrofuran and was added dropwise under ice cooling to 9.4 g (248 mmol) lithium aluminum hydride in 300 ml tetrahydrofuran. The reaction mixture was stirred for lh at room temperature, cooled to 0° C. again and acidified (pH 1-2) by addition of 28% hydrochloric acid solution. After stirring for 5 min, 28% sodium hydroxide solution was added to reach pH 10. The solution was filtered over celite, evaporated and purified by flash chromatography to give 23.6 g (64%) of the title compound as a light brown oil.

Workup

  1. customThe reaction mixture was evaporated
  2. customdried in vacuo for 30 min
  3. dissolutionThe residual oil was dissolved in 100 ml tetrahydrofuran
  4. temperaturecooled to 0° C. again
  5. stirringAfter stirring for 5 min
  6. filtrationThe solution was filtered over celite
  7. customevaporated
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-87ea6a8a4d464e54a5154d40d5000a83
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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