Phenylglycine nitrile → N-(2-cyanomethyl-phenyl)-nicotinamide

HRID 1630830Notes

Reaction equation

HRID 1630830 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]#[N:10].[C:11](Cl)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=1.C(N(C(C)C)CC)(C)C>ClCCl>[C:9]([CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:11](=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=1)#[N:10]

Participants

5

Reactant 3

HCID 76307Phenylglycine nitrileHCID 81531DiisopropylethylamineHCID 82604Nicotinoyl chloride

Product 1

HCID 59534663N-(2-cyanomethyl-phenyl)-nicotinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-aminophenylacetonitrile (5.0 g, 37.1 mmol) and nicotinoyl chloride (7.5 g, 40.8 mmol) are taken up in dry dichloromethane (200 mL) and diisopropylethylamine (12.1 g, 92.7 mmol) is added while cooling the mixture with a cold water bath. The mixture is stirred overnight, whereupon it is washed twice with saturated aqueous sodium bicarbonate. The combined aqueous layer is back-extracted with ethyl acetate. The combined organic phase is dried over MgSO4 and concentrated in vacuo to give a residue, which is purified by silica gel flash chromatography (dichloromethane-methanol, 1:0 to 19:1) to give N-(2-cyanomethyl-phenyl)-nicotinamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.02 (s, 2H), 7.32-7.37 (m, 1H), 7.39-7.44 (m, 2H), 7.50 (d, J=7.1 Hz, 1H), 7.59 (dd, J=8.1, 4.8 Hz, 1H), 8.30-8.33 (m, 1H), 8.78 (dd, J=4.8, 1.5 Hz, 1H), 9.14 (d, J=1.8 Hz, 1H), 10.36 (s, 1H).

Workup

  1. temperaturewhile cooling the mixture with a cold water bath
  2. washis washed twice with saturated aqueous sodium bicarbonate
  3. extractionThe combined aqueous layer is back-extracted with ethyl acetate
  4. dry with materialThe combined organic phase is dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give a residue, which
  7. customis purified by silica gel flash chromatography (dichloromethane-methanol, 1:0 to 19:1)

Sources & evidence

ORD record
ord-6499621671874a06a219692a1221fd10
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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