Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1999-05-06
2000-03-28
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
564445, C07C21100
Patent
active
060433930
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a process for preparing cyclopropylamines from carboxamides and olefins.
Among the important biologically active cyclopropane derivatives, the cyclopropylamines are most important. A number of aminocyclopropane carboxylic acids occur naturally. Recently, many cyclopropylamines have been used as building blocks of novel medicaments (see Pharnakologie und Toxikologie, Wissenschaftsverlag Mannheim, 1993, p. 655). Cyclopropaneamino acids are of interest, for example, as enzyme inhibitors and for other applications in pharmacology and crop protection. Moreover, it is possible to modify the secondary and tertiary structure of peptide chains in a targeted manner by incorporating cyclopropylamines in key positions. By incorporating cyclopropyl groups, latent instability is created in the centre of the peptide in question, which can react with electrophilic or nucleophilic centres of receptors and enzymes (J. Org. Chem. 54 5866 (1989)). To this end, for example, the cyclopropane-analogue 2,3-methanovalin, which has a fixed confirmation, was prepared instead of the important proteinogenic amino acid valin (ibid.).
For other bioactive amines, too, for example for acetylcholine and 2,5-dimethoxy-4-methylamphetamin, it is possible to synthesize the cyclopropane analogues of fixed confirmation, namely in each case as cis- or trans- diastereomer, to study the receptor geometry and the mechanism of action (J. Med. Chem. 17, 1100 (1974); 18, 1027 (1975); 22, 458 (1979); 25, 526 (1982); 26, 817 (1983) and Chem. Pharm. Bull. 27, 1893 (1979)).
The most important routes which are hitherto known for preparing aminocyclopropane derivatives have been compiled in reviews (The Chemistry of the Cyclopropyl Group, Wiley Interscience 1987, 1342 to 1454). However, only a few of these can be employed generally for preparing differently substituted cyclopropylamines.
There is therefore still a need for a generally applicable, rapid and cost-effective process for preparing a broad range of cyclopropylamines.
This invention, accordingly, provides a process for preparing cyclopropylamines of the formula (I) ##STR5## in which R.sup.1 represents hydrogen, optionally substituted C.sub.1 -C.sub.6 -alkyl, optionally substituted C.sub.2 -C.sub.6 -alkenyl, optionally substituted C.sub.3 -C.sub.7 -cycloalk(en)yl, optionally substituted C.sub.6 -C.sub.10 -aryl or optionally substituted C.sub.7 -C.sub.12 -aralkyl and substituted C.sub.1 -C.sub.6 -alkyl, optionally substituted C.sub.2 -C.sub.6 -alkenyl, optionally substituted C.sub.5 -C.sub.7 -cycloalk(en)yl, optionally substituted C.sub.6 -C.sub.10 -aryl or optionally substituted C.sub.7 -C.sub.12 -aralkyl and of R.sup.1 are each defined as R.sup.1, where R.sup.4 may additionally also represent N(H) (C.sub.1 -C.sub.6 -alkyl) or O-C.sub.1 -C.sub.8 -alkyl, or together represent a bridge of the formulae (II) to (V) ##STR6## in which m represents an integer from 2 to 5 and integer from 1 to 4, least 1 and at most 4, and and R.sup.6 together may also represent --CH.sub.2 --CH.sub.2 -- and represent hydrogen, groups may optionally be substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.3 -C.sub.7 -cycloalk(en)yl, C.sub.6 -C.sub.10 -aryl or C.sub.7 -C.sub.12 -aralkyl, ##STR7## in which R.sup.1, R.sup.2 and R.sup.3 are each as defined under formula (I), is reacted with an olefin of the formula ##STR8## in which R.sup.4, R.sup.5 and R.sup.6 are each as defined under formula (I) formula C.sub.5 -C.sub.7 -cycloalkyl and ##STR9## in which R.sup.9 represents straight-chain or branched C.sub.1 -C.sub.6 -alkyl, C.sub.5 -C.sub.7 -cycloalkyl or C.sub.6 -C.sub.10 -aryl, or 1 and the sum q+r =4 and, in the case Y.dbd.V.dbd.O, q represents 3 and r represents zero.
If the radicals R.sup.1 to R.sup.7 represent alkyl and alkenyl groups, these may be straight-chain or branched, the number of the carbon atoms permitting, and this also applies to the alkyl moiety of aralkyl groups.
If the radicals R.sup.1 to R.sup.7 represent substituted alkyl, alkenyl, cycloalk(en)yl, aryl
REFERENCES:
Chaplinski, V, et al Angewandte Chemie. Int. Ed Engl 1996 35. No. 4 pp. 413-414
Bolesov, IG et al Journal of Organic Chemistry of the USSR Bd 10 No. 6 Nov. 1974.
Chaplinski Vladimir
de Meijere Armin
Kourdioukov Alexandre
Bayer Aktiengesellschaft
Gil Joseph C.
Henderson Richard E. L.
Killos Paul J.
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