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

HRID 379409Notes

Reaction equation

HRID 379409 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+:21].[Cl-].[CH2:23]1[CH2:27]OCC1>>[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:21]2[CH2:23][CH2:27][N:3]([CH3:4])[CH2:2][CH2:11]2)=[N:3][CH:4]=1)=[O:7]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 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%

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 (IM 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 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. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-2e28a603c54645aea2ce3671d2ca22e4
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

Loading…