Acetic Acid → 4-(5-Fluoro-2-methyl-4-oxo-4H-chromen-8-yl)-2,6-dimethyl-5-(4-methylpentanoyl)-1,4-dihydropyridine-3-carbonitrile

HRID 557406Notes

Reaction equation

HRID 557406 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([CH:12]=O)=[C:8]2[C:3]=1[C:4](=[O:15])[CH:5]=[C:6]([CH3:14])[O:7]2.[C:16]([CH:18]=[C:19]([O-])[CH3:20])#[N:17].[Na+].[NH2:23][C:24](=[CH:26][C:27](=[O:33])[CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH3:25].C(O)(=O)C>CC(O)C>[F:1][C:2]1[CH:11]=[CH:10][C:9]([CH:12]2[C:26]([C:27](=[O:33])[CH2:28][CH2:29][CH:30]([CH3:31])[CH3:32])=[C:24]([CH3:25])[NH:23][C:19]([CH3:20])=[C:18]2[C:16]#[N:17])=[C:8]2[C:3]=1[C:4](=[O:15])[CH:5]=[C:6]([CH3:14])[O:7]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 574388885-fluoro-2-methyl-4-oxo-4H-chromene-8-carbaldehydeHCID 714061112-Amino-7-methyloct-2-en-4-oneHCID 74083625Sodium 1-cyanoprop-1-en-2-olate

Product 1

HCID 159792204-(5-Fluoro-2-methyl-4-oxo-4H-chromen-8-yl)-2,6-dimethyl-5-(4-methylpentanoyl)-1,4-dihydropyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 100 mg (0.49 mmol) of 5-fluoro-2-methyl-4-oxo-4H-chromene-8-carbaldehyde in 5 ml of 2-propanol is mixed with 50.96 mg (0.49 mmol) of sodium 1-cyanoprop-1-en-2-olate, 75.3 mg (0.49 mmol) of 2-amino-7-methyloct-2-en-4-one and 0.04 ml (0.73 mmol) of acetic acid and stirred under reflux for 3 h. After cooling, the mixture is concentrated. The residue is taken up in dichloromethane and washed with water. The organic phase is dried over sodium sulfate and concentrated. The resulting residue is crystallized from diethyl ether. The yellow crystals are filtered off with suction and purified further on an Analogix cartridge (F12M) (mobile phase: cyclohexane/ethyl acetate 2:1). 75.2 mg (38.1% of theory) of the title compound are obtained.

Workup

  1. temperatureunder reflux for 3 h
  2. temperatureAfter cooling
  3. concentrationthe mixture is concentrated
  4. washwashed with water
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue is crystallized from diethyl ether
  8. filtrationThe yellow crystals are filtered off with suction
  9. custompurified further on an Analogix cartridge (F12M) (mobile phase: cyclohexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-d985b3432eaa4ba784bfb690329183de
Source dataset
uspto-grants-2011_11
Patent number
US08058447B2

Reaction notes

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