Sodium Methoxide → 3-Isopropyl 5-(1-benzhydryl-3-azetidinyl) 2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

HRID 622674Notes

Reaction equation

HRID 622674 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:32]=[CH:33][CH:34]=1)[CH:7]=[C:8]([C:29]([CH3:31])=O)[C:9]([O:11][CH:12]1[CH2:15][N:14]([CH:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:13]1)=[O:10])([O-:3])=[O:2].Cl.[C:36]([CH2:39][C:40]([O:42][CH:43]([CH3:45])[CH3:44])=[O:41])(=[NH:38])[NH2:37].C[O-].[Na+]>C(O)(C)C>[NH2:38][C:36]1[NH:37][C:29]([CH3:31])=[C:8]([C:9]([O:11][CH:12]2[CH2:15][N:14]([CH:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:13]2)=[O:10])[CH:7]([C:6]2[CH:32]=[CH:33][CH:34]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[C:39]=1[C:40]([O:42][CH:43]([CH3:45])[CH3:44])=[O:41]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 12391081Isopropyl amidinoacetate hydrochlorideHCID 544478421-Benzhydryl-3-azetidinyl 2-(3-nitrobenzylidene)acetoacetate

Product 1

HCID 100769753-Isopropyl 5-(1-benzhydryl-3-azetidinyl) 2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylateYield 56.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

1.6 g (0.0035 mole) of 1-benzhydryl-3-azetidinyl 2-(3-nitrobenzylidene)acetoacetate (prepared as described in Preparation 15) and 0.63 g (0.0035 mole) of isopropyl amidinoacetate hydrochloride were dissolved in 40 ml of isopropanol. 0.19 g (0.0035 mole) of sodium methoxide was then added to the mixture, and the mixture was heated under reflux for 4 hours. At the end of this time, the mixture was cooled, and the insoluble material was filtered off. The solvent was then distilled off under reduced pressure, and the residue was dissolved in ethyl acetate. The resulting solution was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography, using a 4:1 by volume mixture of toluene and ethyl acetate as eluent, to give 1.15 g (yield 56%) of the title compound as pale yellow crystals, melting at 104°-107° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hours
  3. temperatureAt the end of this time, the mixture was cooled
  4. filtrationthe insoluble material was filtered off
  5. distillationThe solvent was then distilled off under reduced pressure
  6. dissolutionthe residue was dissolved in ethyl acetate
  7. washThe resulting solution was washed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customThe residue was purified by silica gel column chromatography
  11. additionby volume mixture of toluene and ethyl acetate as eluent

Sources & evidence

ORD record
ord-0b8554de580c4b11af6c66effeb987ad
Source dataset
uspto-grants-1988_09
Patent number
US04772596

Reaction notes

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