Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates

Molecules. 2015 Nov 12;20(11):20341-54. doi: 10.3390/molecules201119697.

Abstract

The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines as without it the reaction does not proceed at all. The aminolysis reaction proceeded regioselectively, as the alkyl ester conjugated with the 1,4-dihydropyridine cycle was not involved in the reaction. Screening of other N-containing bases, such as triethylamine (TEA), pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), imidazole, tetramethyl guanidine (TMG) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as catalysts revealed no activity in the studied reaction.

Keywords: 1,4-dihydropyridines; 1,5,7-triazabicyclo[4.4.0]dec-5-ene; aminolysis; carbamoylmethyl esters; cyclic amines; ethoxycarbonylmethyl esters; secondary amines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Carboxylic Acids / chemistry*
  • Catalysis
  • Dihydropyridines / chemical synthesis
  • Dihydropyridines / chemistry*
  • Esters
  • Solvents / chemistry

Substances

  • Amines
  • Carboxylic Acids
  • Dihydropyridines
  • Esters
  • Solvents
  • 1,4-dihydropyridine