Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1985-10-01
1987-06-02
Brust, Joseph Paul
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C07D23922, C07D23950
Patent
active
046705619
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a process for obtaining the hydrochloric salt of 2,5,6-triamino-4(1H)-pyrimidinone (TAP) with a low content of organic foreign substances by reacting the reduction product of 2,6-diamino-5-nitroso-4(1H)-pyrimidinone (DANP) with hydrogen chloride. The TAP has the Chemical Abstracts Register Number 51 324-37-9, the DANP has got the Chemical Abstracts Register Number 2 387-48-6.
The reduction of DANP which leads to the free TAP base is carried out technically in an aqueous alkaline solution at 40.degree. to 80.degree. C. either No. 49065. The free TAP base being hot is filtered off from the deposited sulfur, and a reaction product consisting substantially of free TAP base and TAP dihydrogen chloride, is separated by salting out with ammonium chloride at a pH of 2; or or noble metals as catalyst according to French Patent document No. FP 955539. The TAP as a slightly soluble reaction product in form of a sulfate, resulting from acidifying the solution to a pH of 2 with sulfuric acid, is deposited in the diluted solution from which the Raney nickel has been filtered off.
Both processes provide reaction products which still contain five to ten mole percent, based on the amount of TAP being present, of foreign organic accompanying substances:
For chemical reactions in an aqueous/alcoholic solution the TAP has to be present in the form of a readily soluble dihydrogen chloride (C. B. Storm, J. org. Chem. 36 (1971), 3925).
According to (a) (Polish Patent document No. 49065) the TAP-di-HCl could be separated from the reaction product by dissolving said reaction product in aqueous hydrochloric acid, and which would also dissolve the foreign organic accompanying substances.
According to Y. Kim, Journal of Heterocyclic Chem. 9 (1972), page 485, TAP-di-HCl can be obtained by reacting TAP sulfate with aqueous barium chloride solution, wherein the solution formed also contains an excess of barium ions in addition to the foreign organic accompanying substances, which renders the solution dangerous from a physiological standpoint.
In chemical reactions of the TAP solutions obtained according in the aforementioned manner, the foreign organic accompanying substances mostly react with the reagents introduced, and thus the endproducts produced, are difficult to purify.
The products prepared from TAP are mostly natural substances or important pharmaceutical components, such as Guanine, Xanthine, Folic acid and Biopterin.
This class of compounds, purines and pteridines, are chemically unstable and may be subjected to partial fragmentation by the application of the necessary purifying procedures, whereby a further impurity and in any case a loss of yield would be expected.
Attempts have already been made to remove the foreign organic accompanying substances from the reduction product of DANP by repeatedly recrystallizing the TAP sulfate from hot 2% sulfuric acid with the aid of activated carbon (Polonovsky et.al. Bull. Soc. Chim. 1946, 80 to 85). Although this method finally achieves the goal intended, said method is complicated and expensive, since TAP sulfate hardly dissolves even in hot 2% sulfuric acid, and to work with large volumes, is unavoidable. Additionally, in a second reaction step, the TAP sulfate so purified still has to be reacted with BaCl.sub.2 to obtain TAP-di-HCl.
Accordingly, the object of the invention is to prepare TAP-di-HCl of the formula (i.e. the tautomeric hydroxy form thereof): ##STR1## with small amounts (i.e. less than 1 mole percent) of foreign organic substances in a technically simple and economic manner, directly from the reduction products of DANP with a single purification process.
It was now found that this problem can be solved by reacting a reduction product of DANP, obtained according to the aforementioned processes (a) or (b), in a reaction medium of hydrogen chloride, water and isopropyl alcohol. The temperature of the reaction medium is between about 60.degree. and 120.degree. C., and the treatment period is between 24 hours at 60.degree. C. and ten minutes at 120.
REFERENCES:
Storm, et al.; J. of Org. Chem., 36, (1971), pp. 3925-3927.
"Journal of Heterocyclic Chem.", 9 (1972), pp. 481-487, Young-Ho Kim et al.
"Bull. Soc. Chim.", 1946, pp. 80-85, Polonovski et al.
Blum Holger
Dreesmann Gernot
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