Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1990-01-12
1991-06-04
Bond, Robert T.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
548551, C07D22310, C07D20727
Patent
active
050215680
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to the art of organic chemistry and, more specifically, to novel compounds, viz. lactam-1-acetic acid carbalkoxymethyl esters and to a method for preparing same. The compounds according to the present invention are intermediate compounds in the synthesis of known biologically active compounds with a peptide bond, for example 2-(2-oxo-1-pyrrolidinylacetamido)acetamide, 2-(2-oxo-4-phenyl-1-pyrrolidinylacetamido)acetamide, 2-(2-oxo-hexahydro-1-azepinylacetamido)acetamide and other compounds.
PRIOR ART
Known in the art are lactam-1-acetic acid esters and various methods for preparing same. For example, known is a method for preparing lactam-1-acetic acid esters from lactams and esters of a monohaloacetic acid using, as metallation agents, dispersed sodium hydroxide in toluene with azeotropically distilling-off water (RO, A, 77162, 77180). The resulting alkyl esters are not employed for the formation of a peptide bond with derivatives of aminoacids. The activated esters of lactam-1-acetic acid employed in the reaction of the formation of a peptide bond with aminoacid derivatives are prepared from lactams in several stages.
Thus, known in the art is a method for preparing lactam-1-acetic acid trichlorophenyl ester by reacting 1-trimethylsilyllactam with bromoacetic acid trichlorophenyl ester in the presence of propyelen oxide (SU, A, 984407); or, also known is a method of condensation of N-hydroxysuccinimide with lactam-1-acetic acid in the presence of dicyclohexylcarbodiimide resulting in the formation of corresponding esters (DD, A, 215539).
DISCLOSURE OF THE INVENTION
The compounds according to the present invention and the method for preparing same are novel and hitherto unknown from the literature.
The present invention is directed to the provision of novel compounds for the peptide synthesis of biologically active compounds by a simplified process with a high yield.
This object is accomplished by that, according to the present invention, novel compounds are claimed, viz. lactam-1-acetic acid carbalkoxymethyl esters of the general formula: ##STR3## wherein with R=H, n=1 or 3, and with B=phenyl, n-1; B.sup.1 is an alkyl.
The lactam-1-acetic acid carbalkoxymethyl esters are stable, viscous, colourles or slightly yellowish liquids, or low-melting white crystalline substances distillable in vacuum. Their structure is verified by methods of IR- and NMR-spectroscopy, elemental analysis or chemical transformations.
The claimed lactam-1-acetic acid carbalkoxymethyl esters are activated esters and, in contrast to known lactam-1-acetic acid alkyl esters, can be used for the formation of a peptide bond under mild conditions with derivatives of aminoacids in the synthesis of known biologically active compounds such as 2(-oxo-1-pyrrolidinylacetamido)acetamide, 2-(2-oxo-4phenyl-1-pyrrolidinylacetamido)acetamide, 2-(2-oxohexahydro-1-azepinylacetamido)acetamide and other compounds. The use of the compounds according to the present invention makes it possible to carry out the formation of a peptide bond without using conventional condensation agents usually employed in such cases, e.g. dicyclohexylcarbodiimide, as well as to elevate the yield of products of the peptide synthesis.
The method for preparing the compounds according to the present invention resides in that lactams of the general formula: ##STR4## wherein with R=H, n=1 or 3, where R=phenyl, n=1
are reacted with an alkali in a medium of aprotic solvents at a temperature within the range of from 70.degree. to 130.degree. C., followed by the addition of an alkyl ester of a monohaloacetic acid to the resulting mixture and isolation of the desired product. In order to simplify the process, as the alkali it is advisable to use potassium hydroxide and as the aprotic solvents--dimethylsulphoxide or a mixture thereof with toluene or benzene. To increase the yield of the desired product, it is advisable that as the alkyl ester of the monohaloacetic acid use be made ethylchloroacetate or ethylbromoacetate.
The meth
REFERENCES:
patent: 4341290 (1982-07-01), Betzing et al.
patent: 4416818 (1983-11-01), Poindexter
patent: 4650878 (1987-03-01), Aschwanden et al.
WO/89/10359, published Nov. 2, 1989, 10 pages.
Baukov Jury I.
Kramarova Evgenia P.
Orlova Natalia A.
Shipov Alexandr G.
Ziemelis Kristap M.
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