Acetic Acid → Isopropyl 5-cyano-4-(5,6-difluoro-2-methyl-4-oxo-4H-chromen-8-yl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate

HRID 557415Notes

Reaction equation

HRID 557415 reaction equation
[F:1][C:2]1[C:11]([F:12])=[CH:10][C:9]([CH:13]=O)=[C:8]2[C:3]=1[C:4](=[O:16])[CH:5]=[C:6]([CH3:15])[O:7]2.[C:17]([CH:19]=[C:20]([O-])[CH3:21])#[N:18].[Na+].[NH2:24]/[C:25](/[CH3:33])=[CH:26]\[C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28].C(O)(=O)C>CC(O)C>[C:17]([C:19]1[CH:13]([C:9]2[CH:10]=[C:11]([F:12])[C:2]([F:1])=[C:3]3[C:8]=2[O:7][C:6]([CH3:15])=[CH:5][C:4]3=[O:16])[C:26]([C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[C:25]([CH3:33])[NH:24][C:20]=1[CH3:21])#[N:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 111372742-Butenoic acid, 3-amino-, 1-methylethyl esterHCID 574388895,6-difluoro-2-methyl-4-oxo-4H-chromene-8-carbaldehydeHCID 74083625Sodium 1-cyanoprop-1-en-2-olate

Product 1

HCID 66991696Isopropyl 5-cyano-4-(5,6-difluoro-2-methyl-4-oxo-4H-chromen-8-yl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 100 mg (0.45 mmol) of 5,6-difluoro-2-methyl-4-oxo-4H-chromene-8-carbaldehyde in 5 ml of 2-propanol is mixed with 46.9 mg (0.45 mmol) of sodium 1-cyanoprop-1-en-2-olate, 63.88 mg (0.45 mmol) of isopropyl 3-aminocrotonate and 0.04 ml (0.67 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 beige-colored crystals are filtered off with suction and dried at 40° C. in a vacuum drying oven. 105.9 mg (57.3% 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 beige-colored crystals are filtered off with suction
  9. customdried at 40° C. in a vacuum
  10. customdrying oven

Sources & evidence

ORD record
ord-b7b10c226ae54a7f9603c8ea8576edf2
Source dataset
uspto-grants-2011_11
Patent number
US08058447B2

Reaction notes

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