1448166-73-1

Upstream product

• 7357-70-2 Cyanothioacetamide 
• 71653-64-0 o-difluoromethoxybenzaldehyde 
• 105-45-3 acetoacetic acid methyl ester 

Downstream Products

• 1447633-38-6 methyl 5-cyano-4-(2-difluoromethoxyphenyl)-6-(methoxycarbonylmethyl)sulfanyl-2-methyl-1,4-di-hydropyridine-3-carboxylate 
• 1447633-44-4 methyl 6-(carboxymethyl)sulfanyl-5-cyano-4-(2-difluoromethoxyphenyl)-2-methyl-1,4-dihydro-pyridine-3-carboxylate 
• 1448166-80-0 methyl 5-cyano-4-(2-difluoromethoxyphenyl)-6-(2-methoxycarbonylethylsulfanyl)-2-methyl-1,4-dihydropyridine-3-carboxylate 

Relevant academic research and scientific papers

Effective method of lipase-catalyzed enantioresolution of 6-alkylsulfanyl-1,4-dihydropyridines

A series of 6-alkylsulfanyl-1,4-dihydropyridines (±)-2 bearing a methoxycarbonylethyl group as a mild easily removable protecting group at S atom have been prepared by alkylation of 6-thioxo-1,4-dihydropyridines 1 with methyl bromopropionate. Candida antarctica lipase B (Novozyme 435, CAL-B) - and Amano Acylase (Aspergillus mellus)-catalyzed kinetic resolution has been investigated in water-saturated diisopropyl ether (IPE) at 25 and 45 °C. After acrylic acid methyl ester as leaving group cleavage and alkylation of formed enantioenriched 1,4-dihydropyridine-6-thiolates (-)-4 and (+)-4, optically active 1,4-dihydropyridines (-)-2, (+)-2, (-)-5 and (+)-5 were obtained in 85-99% enantiomeric excess. The experiments present the 6-(methoxycarbonylethyl)- sulfanyl group as an essentially new enzymatically labile (activating) group. The ester group being 6 bonds remote from the chiral center undergoes easy enzymatic hydrolysis and could be used for kinetic resolution of racemic 1,4-DHPs. This developed method offers access to mild optically active nucleophilic tiolates, which could be easily derivatized with electrophilic reagents.

Synthesis and enantioselective lipase-catalyzed kinetic resolution of methyl 6-(methoxycarbonyl-methyl)sulfanyl-1,4-dihydropyridine-3-carboxylates

A series of methyl 6-(methoxycarbonylmethyl)sulfanyl-1,4-dihydropyridine-3- carboxylates as more lipophilic derivatives of biologically active 6-methylsulfanyl-1,4-dihydropyridine-3-carboxylic acid esters has been prepared by alkylation of 6-thioxo-1,4-dihydropyridines with methyl bromoacetate. The kinetic resolution catalyzed by Candida antarctica lipase B (Novozym 435 ) has been investigated; the enantiomeric excess of the target products reached 70%. The experiments revealed that the 6- (methoxycarbonylmethyl)sulfanyl group is an essentially new activating group, which, being removed by five bonds from the chiral center, undergoes easy enzymatic hydrolysis and could be used for kinetic resolution of racemic 1,4-dihydropyridines.