Isopropyl 4,4,4-Trifluoroacetoacetate → Isopropyl 5-cyano-6-methyl-4-(2-methyl-4-oxo-4H-chromen-8-yl)-2-(trifluoromethyl)-1,4-dihydropyridine-3-carboxylate

HRID 557435Notes

Reaction equation

HRID 557435 reaction equation
[CH3:1][C:2]1[O:3][C:4]2[C:9]([C:10](=[O:12])[CH:11]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[CH:13]=O.[F:15][C:16]([F:27])([F:26])[C:17](=O)[CH2:18][C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20].[NH2:28]/[C:29](/[CH3:33])=[CH:30]\[C:31]#[N:32]>CC(O)C.C(O)(=O)C>[C:31]([C:30]1[CH:13]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[O:3][C:2]([CH3:1])=[CH:11][C:10]3=[O:12])[C:18]([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])=[C:17]([C:16]([F:27])([F:26])[F:15])[NH:28][C:29]=1[CH3:33])#[N:32]

Participants

6

Reactant 3

HCID 586897Isopropyl 4,4,4-TrifluoroacetoacetateHCID 5325263(2Z)-3-Amino-2-butenenitrileHCID 133748832-Methyl-4-oxo-4H-chromene-8-carbaldehyde

Product 1

HCID 66991558Isopropyl 5-cyano-6-methyl-4-(2-methyl-4-oxo-4H-chromen-8-yl)-2-(trifluoromethyl)-1,4-dihydropyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 3776IsopropanolSolvent

Procedure

100 mg (0.53 mmol) of 2-methyl-4-oxo-4H-chromene-8-carbaldehyde are dissolved with 105 mg (0.53 mmol) of isopropyl 4,4,4-trifluoro-3-oxobutanoate, 43.6 mg (0.53 mmol) of 3-aminocrotononitrile and 46 μl (0.79 mmol) of acetic acid in 5 ml of 2-propanol and heated under reflux under argon for 4 h. The solvent is removed in vacuo, and the residue is purified by preparative HPLC. The main product obtained in this way is stirred under reflux in acetic acid overnight. The solution is concentrated and the residue is recrystallized from diethyl ether. 75 mg (33% of theory) of the title compound are obtained as a white solid.

Workup

  1. temperatureheated
  2. temperatureunder reflux under argon for 4 h
  3. customThe solvent is removed in vacuo
  4. customthe residue is purified by preparative HPLC
  5. customThe main product obtained in this way
  6. concentrationThe solution is concentrated
  7. customthe residue is recrystallized from diethyl ether

Sources & evidence

ORD record
ord-82159283c3db441dafd8188a6d083294
Source dataset
uspto-grants-2011_11
Patent number
US08058447B2

Reaction notes

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