Acetic Acid → Ethyl 2-amino-5-cyano-6-methyl-4-(3-phenyl-1,7-naphthyridin-5-yl)-1,4-dihydropyridine-3-carboxylate

HRID 2260829Notes

Reaction equation

HRID 2260829 reaction equation
[C:1]1([C:7]2[CH:8]=[N:9][C:10]3[CH:11]=[N:12][CH:13]=[C:14]([CH:17]=O)[C:15]=3[CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19][C:20]1O[N:23]=[CH:22][CH:21]=1.[Na].Cl.[C:27]([CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])(=[NH:29])[NH2:28].C(O)(=O)C>C(O)C>[NH2:29][C:27]1[NH:28][C:20]([CH3:19])=[C:21]([C:22]#[N:23])[CH:17]([C:14]2[CH:13]=[N:12][CH:11]=[C:10]3[C:15]=2[CH:16]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=[N:9]3)[C:30]=1[C:31]([O:33][CH2:34][CH3:35])=[O:32]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 798335-MethylisoxazoleHCID 5360545SodiumHCID 103539863-Phenyl-1,7-naphthyridine-5-carboxaldehydeHCID 15555354Ethyl 2-carbamimidoylacetate hydrochloride

Product 1

HCID 9931434Ethyl 2-amino-5-cyano-6-methyl-4-(3-phenyl-1,7-naphthyridin-5-yl)-1,4-dihydropyridine-3-carboxylateYield 57.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
50 °C

Procedure

2 g (8.5 mmol) of 3-phenyl-1,7-naphthyridine-5-carboxaldehyde are suspended in 20 ml of ethanol and stirred with 0.7 ml (8.5 mmol) of 5-methylisoxazole. A solution of 196 mg of sodium in 14 ml of ethanol is added and the mixture is stirred for 2 hours at 50° C. 1.42 g of ethyl amidinoacetate hydrochloride and 0.51 ml (8.5 mmol) of acetic acid are added and the mixture is boiled for 16 hours. After cooling, 10 g of silica gel are added and the mixture is concentrated in vacuo. The residue is chromatographed on a silica gel column using toluene/ethyl acetate mixtures. After concentration of the pure fractions, the product is crystallized by trituration with ether. 2 g of crystals are obtained.

Workup

  1. waitthe mixture is boiled for 16 hours
  2. temperatureAfter cooling
  3. addition10 g of silica gel are added
  4. concentrationthe mixture is concentrated in vacuo
  5. customThe residue is chromatographed on a silica gel column
  6. customAfter concentration of the pure fractions, the product is crystallized by trituration with ether

Sources & evidence

ORD record
ord-be7137f45f0b4f94a3ff8f2b42d66415
Source dataset
uspto-grants-1995_12
Patent number
US05478937

Reaction notes

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