Sodium ethoxide → 5-[2-(4-Benzhydryl-1-piperazinyl)ethyl] 3-ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate

HRID 746239Notes

Reaction equation

HRID 746239 reaction equation
[Na].CC[O-].[Na+].[N+:6]([C:9]1[CH:10]=[C:11]([CH:41]=[CH:42][CH:43]=1)[CH:12]=[C:13]([C:38]([CH3:40])=O)[C:14]([O:16][CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][N:22]([CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21][CH2:20]1)=[O:15])([O-:8])=[O:7].Cl.[C:45]([CH2:48][C:49]([O:51][CH2:52][CH3:53])=[O:50])(=[NH:47])[NH2:46]>C(O)C>[NH2:47][C:45]1[NH:46][C:38]([CH3:40])=[C:13]([C:14]([O:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][N:22]([CH:25]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:21][CH2:20]2)=[O:15])[CH:12]([C:11]2[CH:41]=[CH:42][CH:43]=[C:9]([N+:6]([O-:8])=[O:7])[CH:10]=2)[C:48]=1[C:49]([O:51][CH2:52][CH3:53])=[O:50]

Participants

6

Reactant 4

HCID 2723922Sodium ethoxideHCID 5360545SodiumHCID 15555354Ethyl 2-carbamimidoylacetate hydrochlorideHCID 541101302-(4-Benzhydryl-1-piperazinyl)ethyl 2-(3-nitrobenzylidene)acetoacetate

Product 1

HCID 135044795-[2-(4-Benzhydryl-1-piperazinyl)ethyl] 3-ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Sodium (0.20 g) was dissolved in dry ethanol (10 ml) and the thus-obtained sodium ethylate solution was added dropwise to a solution of 2-(4-benzhydryl-1-piperazinyl)ethyl 2-(3-nitrobenzylidene)acetoacetate (4.37 g) and ethyl amidinoacetate hydrochloride (1.42 g) in dry ethanol (10 ml) with stirring under reflux over a period of about 15 minutes. The mixture was further refluxed for 5 minutes. The resulting NaCl was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (120 g). From the eluate with ethyl ether-ethyl acetate (10:1, v/v), there was obtained 5-[2-(4-benzhydryl-1-piperazinyl)ethyl] 3-ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate as a yellow powder. Yield 3.22 g. To a solution of 2.48 g of this product in ethanol was added a solution of oxalic acid in ethanol to give the oxalate as crystals. Yield 2.52 g. Recrystallization from ethanol-ethyl ether gave yellow crystals (1.83 g). m.p. 152°-153° C.

Workup

  1. temperatureunder reflux over a period of about 15 minutes
  2. temperatureThe mixture was further refluxed for 5 minutes
  3. filtrationThe resulting NaCl was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel (120 g)

Sources & evidence

ORD record
ord-733c2a67849a4c4fa9498c034953cdea
Source dataset
uspto-grants-1986_07
Patent number
US04603135

Reaction notes

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