Sulfuric Acid → 4-(2-Methylphenyl)-6-(4-methyl-1-piperazinyl)-3-pyridinecarboxamide

HRID 131113Notes

Reaction equation

HRID 131113 reaction equation
[C:1]([C:3]1[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:22])=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)#[N:2].C1(C)C=CC=CC=1.S(=O)(=O)(O)[OH:31].[OH-].[Na+]>O>[CH3:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:4]1[CH:5]=[C:6]([N:9]2[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]2)[N:7]=[CH:8][C:3]=1[C:1]([NH2:2])=[O:31]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 1140TolueneHCID 14798Sodium HydroxideHCID 113807896-(4-Methyl-piperazin-1-yl)-4-o-tolyl-nicotinonitrile

Product 1

HCID 114837284-(2-Methylphenyl)-6-(4-methyl-1-piperazinyl)-3-pyridinecarboxamideYield 98.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of crude 5-cyano-4-(2-methylphenyl)-2-(4-methylpiperazinyl) pyridine (16.85 g, 57.6 mmol), 18 mL of toluene, and 27 mL (49.7 g, 507 mmol) of concentrated sulfuric acid was heated at 70° C. for 12 hours. The mixture was cooled and quenched with 200 mL of cold H2O. Ethyl acetate was added followed by a solution of 45.6 g (1.14 mol) of sodium hydroxide in 200 mL of H2O. Water (200 mL) was added and the layers were separated. The aqueous layer was extracted several times with 100 mL of ethyl. The organic layers were combined and concentrated to afford 17.55 g (98.1%) of 4-(2-methylphenyl)-6-(4-methylpiperazinyl)-3-pyridinecarboxamide as a colorless solid.

Workup

  1. temperatureThe mixture was cooled
  2. customquenched with 200 mL of cold H2O
  3. additionEthyl acetate was added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted several times with 100 mL of ethyl
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-37ada9ab5fa84acdbc33e8cae08b2aa0
Source dataset
uspto-grants-2008_06
Patent number
US07384939B2

Reaction notes

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