Triethylamine → 3-(2,4-Dimethoxybenzylamino)picolinonitrile

HRID 20106

Reaction equation

HRID 20106 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH2:5][NH2:6].C(N(CC)CC)C.[C:20]([C:22]1[C:27](F)=[CH:26][CH:25]=[CH:24][N:23]=1)#[N:21]>CN(C)C(=O)C>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH2:5][NH:6][C:27]1[C:22]([C:20]#[N:21])=[N:23][CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 5972502,4-DimethoxybenzylamineHCID 70604082-Cyano-3-fluoropyridine

Product 1

HCID 222933003-(2,4-Dimethoxybenzylamino)picolinonitrileYield 73.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

2,4-Dimethoxybenzylamine (3.29 g, 19.7 mmol) and triethylamine (1.99 g, 19.7 mmol) were added sequentially to a solution of 2-cyano-3-fluoropyridine (2.0 g, 16.4 mmol) (Sakamoto et. al., Chem. Pharm. Bull., 1985, 33, 565-71) in N,N-dimethylacetamide (29 mL). The reaction was heated at 80° C. for 4 h, quenched with water and extracted with diethyl ether (3×). The combined organic extracts were washed water, saturated brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography (silica gel, 0-12% ethyl acetate (with 0.1 triethylamine) in dichloromethane gradient elution) to produce the title compound (3.25 g). MS 270.3 (M+1).

Workup

  1. customquenched with water
  2. extractionextracted with diethyl ether (3×)
  3. washThe combined organic extracts were washed water, saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (silica gel, 0-12% ethyl acetate (with 0.1 triethylamine) in dichloromethane gradient elution)

Sources & evidence

ORD record
ord-eb10cc9be3b049d8b11cf9434a42020e
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Linked notes

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