Butanoic acid, 2-[(3-nitrophenyl)methylene]-3-oxo-, 1-methylethyl ester → Azelnidipine

HRID 1713412Notes

Reaction equation

HRID 1713412 reaction equation
C[O-].[Na+].[CH:4]([O:7][C:8](=[O:23])[C:9](=[CH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-:22])=[O:21])[CH:15]=1)[C:10]([CH3:12])=O)([CH3:6])[CH3:5].C(O)(=O)C.[CH:28]([N:41]1[CH2:44][CH:43]([O:45][C:46](=[O:51])[CH2:47][C:48](=[NH:50])[NH2:49])[CH2:42]1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(O)(C)C>[CH:4]([O:7][C:8]([C:9]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-:22])=[O:21])[CH:15]=2)[C:47]([C:46]([O:45][CH:43]2[CH2:42][N:41]([CH:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:44]2)=[O:51])=[C:48]([NH2:49])[NH:50][C:10]=1[CH3:12])=[O:23])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 3951175Butanoic acid, 2-[(3-nitrophenyl)methylene]-3-oxo-, 1-methylethyl esterHCID 10942334Sodium MethoxideHCID 453582921-Benzhydrylazetidin-3-YL 3-amino-3-iminopropanoate acetate

Product 1

HCID 65948AzelnidipineYield 88.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

According to Japanese Examined Patent Publication (Kokoku) No. Hei 3-31715, sodium methoxide (0.27 g) was added to a solution of 2-(3-nitrobenzylidene)acetoacetic acid isopropyl ester (1.39 g) and amidinoacetic acid (1-benzhydryl-3-azetidinyl) ester acetate (1.62 g) in isopropyl alcohol (80 ml) and the mixture was heated under reflux for 4 hours. After the reaction mixture was cooled, insoluble material was removed and the solvent was evaporated under reduced pressure. The thus obtained residue was dissolved in ethyl acetate and the mixture was washed with water, followed by drying over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was subjected to silica gel column chromatography (toluene:ethyl acetate=3:1) to obtain pale yellow (±)-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-(1-diphenylmethylazetidin-3-yl) ester 5-isopropyl ester (2.17 g, 74%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hours
  3. temperatureAfter the reaction mixture was cooled
  4. custominsoluble material was removed
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe thus obtained residue was dissolved in ethyl acetate
  7. washthe mixture was washed with water
  8. dry with materialby drying over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4f45a28a2d2a4a0c87ad9c6b8c2cd641
Source dataset
uspto-grants-2010_09
Patent number
US07795281B2

Reaction notes

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