Acetic Acid → 4-(4-Cyano-2-methoxyphenyl)-2,8-dimethyl-5-oxo-1,4,5,6-tetrahydro-1,6-naphthyridine-3-carbonitrile

HRID 1951403Notes

Reaction equation

HRID 1951403 reaction equation
[CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=1[O:11][CH3:12])=O.[C:13]([CH:15]=[C:16]([O-])[CH3:17])#[N:14].[Na+].[NH2:20][C:21]1[C:26]([CH3:27])=[CH:25][NH:24][C:23](=[O:28])[CH:22]=1.C(O)(=O)C>CC(O)C>[C:7]([C:6]1[CH:9]=[CH:10][C:3]([CH:1]2[C:22]3[C:23](=[O:28])[NH:24][CH:25]=[C:26]([CH3:27])[C:21]=3[NH:20][C:16]([CH3:17])=[C:15]2[C:13]#[N:14])=[C:4]([O:11][CH3:12])[CH:5]=1)#[N:8]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 132957324-Amino-5-methylpyridin-2(1H)-oneHCID 166592514-Formyl-3-methoxybenzonitrileHCID 74083625Sodium 1-cyanoprop-1-en-2-olate

Product 1

HCID 674158664-(4-Cyano-2-methoxyphenyl)-2,8-dimethyl-5-oxo-1,4,5,6-tetrahydro-1,6-naphthyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

1773 mg (11.0 mmol) of 4-formyl-3-methoxybenzonitrile are dissolved with 1156 mg (11.0 mmol) of sodium 1-cyanoprop-1-en-2-olate, 1366 mg (11.0 mmol) of 4-amino-5-methylpyridin-2(1H)-one [Bisagni, E., Hung, N. C., Synthesis, 765-766 (1984)] and 945 μl (16.5 mmol) of acetic acid in 50 ml of 2-propanol and heated at the reflux temperature under argon for 20 h. After cooling, the reaction mixture is filtered and the precipitate is washed with 2-propanol and diethyl ether. The crude product is dissolved in 800 ml of dichloromethane/methanol by heating and, after addition of 500 ml of ethyl acetate, again concentrated to a volume of 50 ml. The precipitated product is filtered off and washed with ethyl acetate and diethyl ether. Drying under high vacuum results in 3.63 g (99% of theory) of the title compound in the form of yellowish crystals.

Workup

  1. temperatureheated at the reflux temperature under argon for 20 h
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture is filtered
  4. washthe precipitate is washed with 2-propanol and diethyl ether
  5. dissolutionThe crude product is dissolved in 800 ml of dichloromethane/methanol
  6. temperatureby heating
  7. additionafter addition of 500 ml of ethyl acetate
  8. concentrationagain concentrated to a volume of 50 ml
  9. filtrationThe precipitated product is filtered off
  10. washwashed with ethyl acetate and diethyl ether
  11. customDrying under high vacuum

Sources & evidence

ORD record
ord-4e86f5eeb2244ccfa420c30ed06b7ad0
Source dataset
uspto-grants-2013_03
Patent number
US08404709B2

Reaction notes

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