Methanol → 5-(4-Methoxyphenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 11321

Reaction equation

HRID 11321 reaction equation
[H-].[Na+].CN(C)C=[C:6]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)[C:7](=O)[CH3:8].COC(C1C(C2C=CC=CC=2Cl)C(C(OC)=O)=C(C)[NH:25][C:24]=1COCCN1C(=O)C2C(=CC=CC=2)C1=O)=O.[CH3:56]O.[CH3:58][N:59](C)[CH:60]=[O:61]>>[CH3:17][O:16][C:13]1[CH:12]=[CH:11][C:10]([C:6]2[CH:7]=[C:8]([C:24]#[N:25])[C:60](=[O:61])[NH:59][C:58]=2[CH3:56])=[CH:15][CH:14]=1

Participants

6

Reactant 5

HCID 887MethanolHCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 112609924-(2-Chlorophenyl)-2-[[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy]methyl]-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic Acid 3,5-Dimethyl EsterHCID 539901024-Dimethylamino-3-(4-methoxyphenyl)-3-buten-2-one

Product 1

HCID 133747585-(4-Methoxyphenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrileYield 82%

Procedure

To a stirred solution of sodium hydride (60% dispersion in mineral oil, 4.5 g, 112 mmol) in N,N-dimethylformamide (100 mL) was added dropwise at 0° C. a solution of crude 4-dimethylamino-3-(4-methoxyphenyl)-but-3-en-2-one (3) from the previous step, 2-cyano-acetamide (4, 4.75 g, 56.5 mmol) and methanol (4.54 mL, 112 mmol) in N,N-dimethylformamide (50 mL). The reaction mixture was stirred at ambient temperature for 15 min and then at 95° C. for 18 h. After cooling to ambient temperature most of the solvent was removed under reduced pressure. The residue was hydrolysed with saturated aqueous ammonium chloride solution (100 mL). The precipitated solid was collected by filtration with suction, rinsed with water and diethyl ether and dried under vacuum to give 5-(4-methoxy-phenyl)-6-methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (5) as a brownish solid (10.0 g, 82% yield over two steps, 99% pure by LC-MS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.70 (s, 1H); 7.19 (m, 2H); 6.72 (m, 2H); 3.73 (s, 3H); 1.71 (s, 3H).

Workup

  1. waitat 95° C. for 18 h
  2. temperatureAfter cooling to ambient temperature most of the solvent
  3. customwas removed under reduced pressure
  4. filtrationThe precipitated solid was collected by filtration with suction
  5. washrinsed with water and diethyl ether
  6. customdried under vacuum

Sources & evidence

ORD record
ord-ba1febf7ca664aec9fbf4db68eca4f2b
Source dataset
uspto-grants-2006_08
Patent number
US07098211B2

Linked notes

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