Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
2000-04-26
2000-12-19
Stockton, Laura L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
564189, C07D23502
Patent
active
061629235
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the new process for the preparation of compounds of general formula (I)--wherein R.sup.1 means hydrogen atom or alkyl group of 1-6 carbon atoms--, and to the compounds of general formula (IV)--wherein R means hydrogen atom or alkyl group of 1-4 carbon atoms and R.sup.1 is the same as defined above.
Compounds of general formula (I) are intermediates of compounds with angiotensin-II antagonist activity which are described in Hungarian Patent, No. 211.839 and in the equivalent U.S. Pat. No. 5,270,317.
The above patents, among others, describe a hypotetic reaction route, "reaction scheme B", by this route compounds of general formula (I) might be synthetised from amino-acylamides and ortho esters in acidic medium. In the above specifications this hypothetic reaction route is not demonstrated by examples.
For one skilled in the art, in the knowledge of the prior, this hypothetic reaction route, which applies acidic medium, does not seem to be feasible, since it is known that ortho esters suffer decomposition on the effect of acids/Houben-Weyl Band VI/3 S 315 (1965)/. It is well-known, too, that the lone-pair of electron of primary amines in acidic medium is not available for further reactions, as it takes part in the salt formation. It is also known, that in acidic medium primary amines and ortho esters also give rise to N-aryl- N-alkylformamides, from which the compounds of general formula (I) may not be formed/J. Am. Chem. Soc. 78 p 4778 (1956)/.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 describes the imidazolone products of formula (I), the reactants of formulas (II) and (III) and the intermediates of formula (IV).
In the knowledge of the above we aimed to find a process for the preparation of compounds of general formula (I) which proceeds in good yield and results pure product. We found that if the compound of formula (II) is reacted with a compound of general formula (III)--wherein R means an alkyl group of 1-4 carbon atoms and R.sup.1 is the same as defined above--, by heating their neutral mixtures at reflux temperature, and the resulting compound of general formula (IV)--wherein R and R.sup.1 are the same as defined above--, is cyclized into the compound of general formula (I) by further elevating the temperature of the neutral pH mixture, and if desired, the compound of general formula (I) is transformed into its salt, or the compound of general formula (I) is liberated from its salt, then the compounds of general formula (I) are obtained in very pure condition, in almost theoretical yields, even applying just equivalent amounts of reactants.
Our invention furthermore relates to the new compounds of general formula (IV) which are useful intermediates in the process described above.
According to a preferred embodiment of the invention the compound of formula (II) is mixed with a compound of general formula (III), the reaction is carried out at the boiling point of the mixture, the resulting compound of general formula (IV), optionally without isolation, is then cyclized by enhancing the temperature of the reaction mixture to 110-160.degree. C., in neutral reaction medium, under conditions of distillation or vacuum distillation. When the reaction mixture containing the resulting compounds of general formula (I) is acidified, the compounds compounds of general formula (I) are obtained in the form of their acid addition salt.
The compound of formula (II) can be synthetised as described in the above two patents in Examples 2a and 2b, whereas the compounds of general formula (III) can be prepared according to J. Am. Chem. Soc. 68 p 1923 (1946).
Further details of our process are illustrated by the following examples, without limiting our claims to the content of examples.
EXAMPLE 1
2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-one-monohydrochloride
20 g (0.156 mol) of 1-aminocyclopentane-1-carboxamide and 31 g (0.19 mol) of trimethyl orthovalerate are refluxed at 70-80.degree. C. inner temperature for 1 hour. The condenser is then changed to a "No hold up" condenser, while heating and
REFERENCES:
patent: 5270317 (1993-12-01), Bernhart et al.
Bernhart et al., Journal of Medicinal Chemistry, vol. 36,No. 22, (1993), pp. 3371-3380.
Schollkopf et al., Liebigs Ann. Chem. No. 3, (1981), pp. 439-458.
Brunken et al., Chem. Ber., vol. 89, No. 6, Feb. 2, (1956), pp. 1363-1373.
Khokhlov et al., Journal of Medicinal Chemistry, vol. 54, No. 12, (1984), pp. 2414-2415.
Martinez et al., Journal of Molecular Structure, vol. 75, No. 2, (1981). pp. 241-254.
Schipper et al., Journal of American Chemical Society, vol. 74, (1952), pp. 350-353.
Houben-Weyl, Band VI/3, (1965), pp. 315-317.
Roberts et al., Journal of American Society, vol. 78, (1956), pp. 4778-4781
McElvain et al., Journal of American Chemical Society, vol. 68, (1946), pp. 1922-1925.
Gajary Antal
Huszar Csaba
Kis-Tamas Attila
Nemeth Attila
Pali Lajosne
Sanofi-Synthelabo
Stockton Laura L.
LandOfFree
Process for the preparation of imidazolones does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of imidazolones, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of imidazolones will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-272144