Cyanoacetic acid → 2-cyano-N-(4-methoxypyridin-3-yl)acetamide

HRID 869118Notes

Reaction equation

HRID 869118 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[NH2:9].[C:10]([CH2:12][C:13](O)=[O:14])#[N:11].Cl.C(N=C=NCCCN(C)C)C>C1COCC1.CN(C1C=CN=CC=1)C>[C:10]([CH2:12][C:13]([NH:9][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:3]=1[O:2][CH3:1])=[O:14])#[N:11]

Participants

6

Reactant 3

HCID 9740Cyanoacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 52003433-Amino-4-methoxypyridine

Product 1

HCID 904089092-cyano-N-(4-methoxypyridin-3-yl)acetamideYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4-Methoxypyridin-3-amine (22 g, 177.2 mmol) and 2-cyanoacetic acid (19.60 g, 230.4 mmol) were slurried in THF (1 L). The mixture was cooled in an ice bath and DMAP (28.15 g, 230.4 mmol) was added followed by 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (50.95 g, 265.8 mmol). The mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was partially concentrated, then diluted with ethyl acetate/water. The organic phase was isolated and washed with saturated NaHCO3, then brine, dried (MgSO4), filtered and concentrated. The residue was slurried in ether/petrol to give 2-cyano-N-(4-methoxypyridin-3-yl)acetamide 8 as a yellow solid (26.4 g, 78%). LC-MS (M+H)+ 192.0; 1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 8.86 (s, 1H), 8.28 (d, 1H), 7.15 (d, 1H), 4.00 (s, 2H), 3.92 (s, 3H).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. concentrationThe mixture was partially concentrated
  3. additiondiluted with ethyl acetate/water
  4. customThe organic phase was isolated
  5. washwashed with saturated NaHCO3
  6. dry with materialbrine, dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8e0a3d4296d246a59af0cadd99f9a344
Source dataset
uspto-grants-2015_03
Patent number
US08969360B2

Reaction notes

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