Water → 3-Ethyl-6-methyl-5-[5-(pyridine-2-carbonyl)-thiophen-2-yl]-1H-pyridin-2-one

HRID 1921546Notes

Reaction equation

HRID 1921546 reaction equation
[CH2:1]([C:3]1[C:4](=[O:15])[NH:5][C:6]([CH3:14])=[C:7]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=1)[CH3:2].[Li]CCCC.CON(C)[C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1)=[O:25].O>C1COCC1>[CH2:1]([C:3]1[C:4](=[O:15])[NH:5][C:6]([CH3:14])=[C:7]([C:9]2[S:10][C:11]([C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[O:25])=[CH:12][CH:13]=2)[CH:8]=1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11829796N-Methoxy-N-methylpicolinamideHCID 674922683-ethyl-6-methyl-5-thiophen-2-yl-1H-pyridin-2-oneHCID 178418339Butyllithium

Product 1

HCID 674923353-Ethyl-6-methyl-5-[5-(pyridine-2-carbonyl)-thiophen-2-yl]-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 3-ethyl-6-methyl-5-thiophen-2-yl-1H-pyridin-2-one prepared in accordance with the procedures of Example 24, Step 3 (100 mg, 0.456 mmol) in anhydrous THF (3 ml) is cooled to −78° C., and n-BuLi (2.5 M in hexane, 0.4 ml, 1 mmol) is added. The resulting dark green mixture is stirred for 20 min, and then N-methoxy-N-methylpyridine-2-carboxamide (83 mg, 0.5 mmol) in THF (1 ml) is added. The reaction mixture is then added to water (5 ml) and extracted with ethyl acetate. The organic phases are washed and dried, and the residue is purified on silica gel. The product is dissolved in a minimal amount of methanol and treated with HCl in diethyl ether. The resulting brown precipitate is filtered off with suction and dried (12 mg, as hydrochloride). MS: m/e=325 (M+H). 1H-NMR (D6-DMSO, δ ppm) 11.85 (s, 1H); 8.81 (d, 1H); 8.30 (d, 1H); 8.12 (m, 2H); 7.71 (m, 1H); 7.44 (s, 1H); 7.29 (d, 1H) 3.37 (m, 2H); 2.50 (s, 3H); 1.14 (t, 3H, J=7.4 Hz).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phases are washed
  3. customdried
  4. customthe residue is purified on silica gel
  5. dissolutionThe product is dissolved in a minimal amount of methanol
  6. additiontreated with HCl in diethyl ether
  7. filtrationThe resulting brown precipitate is filtered off with suction
  8. dry with materialdried (12 mg, as hydrochloride)

Sources & evidence

ORD record
ord-eef57f6747704df3a43ef20d95ad91eb
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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