O-Toluidine → N,N-diethyl-2-(o-tolylamino)nicotinamide

HRID 1801494Notes

Reaction equation

HRID 1801494 reaction equation
Cl[C:2]1[N:14]=[CH:13][CH:12]=[CH:11][C:3]=1[C:4]([N:6]([CH2:9][CH3:10])[CH2:7][CH3:8])=[O:5].[NH2:15][C:16]1[C:17]([CH3:22])=[CH:18][CH:19]=[CH:20][CH:21]=1.[H-].[Na+]>O1CCOCC1.ClCCl>[CH2:7]([N:6]([CH2:9][CH3:10])[C:4](=[O:5])[C:3]1[CH:11]=[CH:12][CH:13]=[N:14][C:2]=1[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])[CH3:8]

Participants

6

Reactant 3

HCID 7242O-ToluidineHCID 24758Sodium hydrideHCID 44659442-Chloro-N,N-diethylnicotinamide

Product 1

HCID 66718830N,N-diethyl-2-(o-tolylamino)nicotinamideYield 44.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-N,N-diethylnicotinamide (10.0 g, 47.2 mmol) and o-toluidine (5.0 g, 47.2 mmol) in 1,4-Dioxane (50 mL) was added sodium hydride (60%, 4.72 g, 118 mmol). After addition, the reaction mixture was heated at 100° C. for 2 hours. The reaction mixture was then cooled to room temperature, diluted with dichloromethane (100 mL), washed with water (3×50 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by flash chromatography (SiO2, 50% hexane in ethyl acetate) to afford the desired product, N,N-diethyl-2-(o-tolylamino)nicotinamide (6.0 g) as a yellow oil. LCMS: 284 [M+H].

Workup

  1. additionAfter addition
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. washwashed with water (3×50 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash chromatography (SiO2, 50% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-5dd41413d1a94658a1093890ba1d8696
Source dataset
uspto-grants-2013_01
Patent number
US08349827B2

Reaction notes

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