Sodium Hydroxide → (RS)-6-(4-Methyl-piperazin-1-yl)4-o-tolyl-4,5-dihydro-pyridine-3-carboxylic acid methylamide

HRID 380745Notes

Reaction equation

HRID 380745 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[C:12]1([CH3:20])[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Mg]Cl.[NH4+].[Cl-].[CH3:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.[OH-].[Na+]>C1COCC1>[CH3:9][NH:8][C:6]([C:5]1[CH:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH3:20])[CH2:11][C:2]([N:27]2[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]2)=[N:3][CH:4]=1)=[O:7]

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 25517Ammonium Chloride2×HCID 531671-MethylpiperazineHCID 123642306-Chloro-N-methylnicotinamideHCID 178424304HCID 178424304, compound

Product 1

HCID 15481064(RS)-6-(4-Methyl-piperazin-1-yl)4-o-tolyl-4,5-dihydro-pyridine-3-carboxylic acid methylamideYield 94.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3.0 g (17.6 mmol) 6-chloro-N-methyl-nicotinamide in 42.0 ml THF was treated at 4° C. dropwise over 15 min. with 43.8 ml (43.8 mmol) o-tolylmagnesiumchloride-solution (1M in THF). The reaction mixture was stirred for 2 h at r.t., cooled to 0° C. and treated dropwise with 50 ml 5% aqueous NH4Cl. The aqueous phase was separated and extracted twice with toluene and the organic phases were washed twice with 5% aqueous NH4Cl. The combined organic phases were dried over Na2SO4 and filtrated. The filtrate was treated with 9.8 ml (88.3 mmol) 1-methylpiperazine and stirred for 1.5 h at r.t. The reaction mixture was treated with 40 ml 5% aqueous NH4Cl and the pH adjusted with NaOH (28%) to 10. The aqueous phase was separated and extracted twice with CH2Cl2 and the organic phases were washed twice with brine. The combined organic phases were dried over Na2SO4 and filtrated. The solvent was removed under reduced pressure to yield 5.4 g (94.6 %) product as yellowish crystals, m.p. 137.0-138.0° C.

Workup

  1. temperaturecooled to 0° C.
  2. customThe aqueous phase was separated
  3. extractionextracted twice with toluene
  4. washthe organic phases were washed twice with 5% aqueous NH4Cl
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltrated
  7. stirringstirred for 1.5 h at r.t
  8. customThe aqueous phase was separated
  9. extractionextracted twice with CH2Cl2
  10. washthe organic phases were washed twice with brine
  11. dry with materialThe combined organic phases were dried over Na2SO4
  12. filtrationfiltrated
  13. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-a47a98db879b4dce9ae4ffd7e7020b57
Source dataset
uspto-grants-2001_10
Patent number
US06303790B1

Reaction notes

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