skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 3-Amino-2-carbamoyl-4,6-diphenyl-4,5- and -4,7-dihydrothieno-(2,3-b)pyridines

Abstract

The treatment of piperidinium salts of 3-cyano-1,4-dihydropyridine-2-thiols with alkyl halides leads to 2-alkylthio-3-cyano-1,4-dihydropyridines. The authors have shown that alkylation of the piperidinium salt of 4,6-diphenyl-3-cyano-1,4-dihydropyridine-2-thiol with iodoacetamide gives carbamoylmethylthio derivative II, which, by the action of an equimolar amount of a base with heating to 50-60/sup 0/C, gives a mixture of 3-amino-2-carbamoyl-4,6-diphenyl-4,7-dihydrothieno(2,3-b)pyridine and 3-amino-2-carbamoyl-4,6-diphenyl-4,5-dihydrothieno(2,3-b)-pyridine in a ratio of 1:1. In the presence of excess base the principal product is IV. It was established by PMR spectroscopy that dihydropyridine II initially undergoes cyclization to 4,7-dihydrothienopyridine III, which then undergoes isomerization to 4,5-dihydrothienopyridine IV. Acidification of a solution of IV in d/sub 6/-DMSO gives rise to reverse isomerization.

Authors:
; ;
Publication Date:
Research Org.:
Institute of Organic Synthesis, Riga (USSR)
OSTI Identifier:
7169314
Resource Type:
Journal Article
Resource Relation:
Journal Name: Chem. Heterocycl. Compd. (Engl. Transl.); (United States); Journal Volume: 23:4; Other Information: Translated from Khim. Geterotsikl. Soedin.; 23: No. 4, 563-564(Apr 1987)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; 74 ATOMIC AND MOLECULAR PHYSICS; PYRIDINES; DEHYDROCYCLIZATION; ISOMERIZATION; NMR SPECTRA; ACIDIFICATION; ALKYLATION; AMINES; CHEMICAL SHIFT; COUPLING CONSTANTS; DEUTERATION; DEUTERIUM COMPOUNDS; DMSO; ISOTOPE EFFECTS; J-J COUPLING; ORGANIC SULFUR COMPOUNDS; SYNTHESIS; AZINES; CHEMICAL REACTIONS; COUPLING; HETEROCYCLIC COMPOUNDS; HYDROGEN COMPOUNDS; INTERMEDIATE COUPLING; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; SPECTRA; SULFOXIDES; 400201* - Chemical & Physicochemical Properties; 640302 - Atomic, Molecular & Chemical Physics- Atomic & Molecular Properties & Theory

Citation Formats

Krauze, A.A., Liepin'sh, E.E., and Dubur, G.Ya. 3-Amino-2-carbamoyl-4,6-diphenyl-4,5- and -4,7-dihydrothieno-(2,3-b)pyridines. United States: N. p., 1987. Web. doi:10.1007/BF00546753.
Krauze, A.A., Liepin'sh, E.E., & Dubur, G.Ya. 3-Amino-2-carbamoyl-4,6-diphenyl-4,5- and -4,7-dihydrothieno-(2,3-b)pyridines. United States. doi:10.1007/BF00546753.
Krauze, A.A., Liepin'sh, E.E., and Dubur, G.Ya. 1987. "3-Amino-2-carbamoyl-4,6-diphenyl-4,5- and -4,7-dihydrothieno-(2,3-b)pyridines". United States. doi:10.1007/BF00546753.
@article{osti_7169314,
title = {3-Amino-2-carbamoyl-4,6-diphenyl-4,5- and -4,7-dihydrothieno-(2,3-b)pyridines},
author = {Krauze, A.A. and Liepin'sh, E.E. and Dubur, G.Ya.},
abstractNote = {The treatment of piperidinium salts of 3-cyano-1,4-dihydropyridine-2-thiols with alkyl halides leads to 2-alkylthio-3-cyano-1,4-dihydropyridines. The authors have shown that alkylation of the piperidinium salt of 4,6-diphenyl-3-cyano-1,4-dihydropyridine-2-thiol with iodoacetamide gives carbamoylmethylthio derivative II, which, by the action of an equimolar amount of a base with heating to 50-60/sup 0/C, gives a mixture of 3-amino-2-carbamoyl-4,6-diphenyl-4,7-dihydrothieno(2,3-b)pyridine and 3-amino-2-carbamoyl-4,6-diphenyl-4,5-dihydrothieno(2,3-b)-pyridine in a ratio of 1:1. In the presence of excess base the principal product is IV. It was established by PMR spectroscopy that dihydropyridine II initially undergoes cyclization to 4,7-dihydrothienopyridine III, which then undergoes isomerization to 4,5-dihydrothienopyridine IV. Acidification of a solution of IV in d/sub 6/-DMSO gives rise to reverse isomerization.},
doi = {10.1007/BF00546753},
journal = {Chem. Heterocycl. Compd. (Engl. Transl.); (United States)},
number = ,
volume = 23:4,
place = {United States},
year = 1987,
month =
}
  • The alkylation of piperidinium salts of substituted 1,4-dihydropyridine-2-thiols with chloroacetonitrile or iodoacetamide gave 2-cyanomethylthio- and 2-carbamoylmethylthio-substituted 6-methyl-4-acryl(pyridyl)-5-ethoxycarbonyl-3-cyano-1,4-dihydropyridines, which undergo intramolecular cyclization in basic media to give 3-amino-6-methyl-4-aryl(pyridyl)-5-ethoxycarbonyl-2-cyano(carbamoyl)-4,7-dihydrothieno(2,3-b)pyridines.
  • One of the greatest bottlenecks in producing recombinant proteins in Escherichia coli is that over-expressed target proteins are mostly present in an insoluble form without any biological activity. N-carbamoyl-D-amino-acid amidohydrolase (DCase) is an important enzyme involved in semi-synthesis of ╬▓-lactam antibiotics in industry. In this study, in order to determine the amino acid sites responsible for solubility in DCase, error-prone PCR and DNA shuffling techniques are applied to randomly mutate its encoding sequence, followed by an efficient screening based on structural complementation. Several mutants of DCase with reduced aggregation are isolated. Solubility tests of these mutants and several other mutantsmore » generated by site-directed mutagenesis indicate that three amino acid residues of DCase (A18, Y30 and K34) are related to the protein solubility in DCase. In silico structural modeling analyses further suggest that hydrophilicity and/or negative charge at these three residues may be responsible for the increased solubility of DCase proteins in E. coli. Based on the information, multiple engineering designated mutants were constructed by site-directed mutagenesis; among them, a triple mutant A18T/Y30N/K34E (named as DCase-M3) can be over-expressed in E. coli with up to 80% of DCase-M3 protein as soluble. DCase-M3 is purified to homogeneity and a comparative analysis with WT DCase demonstrates that DCase-M3 enzyme is similar to the native DCase in terms of its kinetic and thermodynamic properties. The study provides new insights on recombinant protein solubility in E. coli.« less
  • The synthesis of o-, m, and p-((trifluoroethyl)amino)pyridine by diborane/tetrahydrofuran reduction of the corresponding trifluoroacetamide is described. The yields were 52%, 83%, and 76%, respectively. The synthesis, in 53% yield, of 2,2,2-trifluoro-N-(4-pyridyl)acetamide is also described.
  • The reaction of 2-(({alpha}-methylbenzylidene)amino)pyridine (L{sub 1}) with RhCl(PPh{sub 3}){sub 3} resulted in the formation of cis-(Cl(PPh{sub 3}){sub 2}(L{sub 1})Rh{sup I}){center dot}S (1, S = solvent). The reaction of 2-(({alpha}-(4-methoxyphenyl)benzylidene)amino)pyridine (L{sub 2}) with Rh{sub 2}Cl{sub 2}(CO){sub 4} (4) under identical conditions resulted in the formation of cis-(Cl(CO){sub 2}(L{sub 2})Rh{sup I}) (2). The ligand L{sub 1} when treated with the same Rh complex 4 at 90{degree}C in an autoclave for 18 h resulted in the formation of (Cl(CO)(L{sub 1}-H)Rh{sup II}){sub 2} (3). Compound 1 crystallized in the triclinic space group P{bar 1} with Z = 2 and lattice parameters a = 10.9817more » (8), b = 12.2447 (12), c = 17.800 (3) {angstrom}, {alpha} = 94.221 (10), {beta} = 101.770 (9), {gamma} = 92.022 (7){degree}, V = 2333.8 (4) {angstrom}{sup 3}. Compound 2 crystallized in the monoclinic space group P2{sub 1}/c with Z = 4 and lattice parameters a = 10.845 (6), b = 11.161 (6), c = 17.161 (9) {angstrom}, {beta} = 86.61 (1){degree}, V = 2073.58 {angstrom}{sup 3}. Compound 3 crystallized in the monoclinic space group P2{sub 1}/c with Z = 4 and lattice parameters a = 8.0708 (16), b = 20.907 (6), c = 16.373 (2) {angstrom}, {beta} = 90.078 (14){degree}, V = 2762.6 (1.0) {angstrom}{sup 3}. The structures of the complexes reported are compared and contrasted with analogous complexes of rhodium.« less