CH417618A - Process for the preparation of new pyrazolo (3,4-d) pyrimidines - Google Patents

Description

  

      Process for the preparation of new pyrazolo [3,4-d] -pvrimidines The invention relates to the preparation of new 2-substituted pyrazolo [3,4-d] pyrimidines, namely 2-R-4-R'-6-R "- Pyrazolo [3,4-d] pyrimidines, in which R is a substituent, preferably an alkyl, cycloalkyl,

          Hydroxymederatkyl- or Halo- genniederalkykest represents such. B. a methyl, ethyl, isopropyl, butyl, amyl, hexyl, cyclopentyl or cyclohexyl radical, R 'the NI-1,

  -Group means and R "has the same meaning as R 'or represents hydrogen or a lower alkyl radical, and their tautomeric forms and the salts of these compounds.



  The new compounds have valuable pharmacological properties. They show anti-tumor and also antibacterial and antifungal properties.

   The new compounds can therefore be used as remedies. But they are also valuable intermediate products for the manufacture of medicines. The free or etherified mercapto groups in the new compounds can be exchanged for amine groups.



  The compounds of the formula are particularly valuable
EMI0001.0066
    and their salts, in which R represents a lower alkyl radical, especially a methyl, ethyl, propyl, butyl or amyl radical.



  The process according to the invention consists in reacting 1-R-3-amino-pyrazole-4-nitriles with corresponding functional acid derivatives containing the NH2 group. Fomamide, urea, thiourea or guandin are primarily used for reaction with the amino groups.



  The aminopyrazoles are condensed to the pyrazolopyrimidines preferably at temperatures above 100, if appropriate in the presence of diluents and / or condensing agents in an open or closed vessel.



  Depending on the substituents present in the process products, various salts can be prepared. If they have acidic groups, metal salts can be obtained, e.g. B. by dissolving in alkaline solutions. Basic compounds form salts with inorganic or organic acids.

   Examples of salt-forming acids are: hydrohalic acids, sulfuric acids, phosphoric acids, nitric acid, perchloric acid;

          aliphatic, acyclic, aromatic and heterocyclic carboxylic or sulfonic acids, such as formic, acetic, propionic, oxalic, amber, glycol, milk, apple, wine, lemon, ascorbic, Oxymaleic, dioxymaleic or pyruvic acid;

          Phenylacetic, benzoic, p-aminobenzoic, anthranu, p-oxybenzoic, salicylic or p aminosalicylic acid; Methanesulphonic, ethanesulphonic, oxyethanesulphonic, ethylene sulphonic acid; Toluenesulfonic, naphthalenesulfonic or sulfanilic acid;

          Methione, tryptophan, lysine or arginine.



  The new, pharmacologically valuable compounds, their salts or corresponding mixtures can, for. B. in, form. find pharmaceutical preparations Ver use. These contain the named compounds mixed with one for enteral,

            parenteral or. topical application suitable pharmaceutical organic or inorganic carrier material. For the same substances come into question that do not react with the compounds described, such as.

   B. gelatin, milk sugar, starch, magnesium stereate, talc, vegetable oils, water, benzyl alcohols, gum, polyalkylene glycols, cholesterol: or other known excipients. The pharmaceutical preparations can e.g.

   B. as tablets, coated tablets, or in liquid form as solutions, suspensions or emulsions. If necessary, they are sterilized and / or

       or contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsifiers. They can also contain other therapeutically valuable substances. The preparations can be obtained by conventional methods.



  The 1-substituted pyrazoles required as starting materials can, according to Swiss patent specification No.

   396 011 are obtained by adding α-cyano-β-oxopropionic acids, optionally in the form of their functional reactive acid and / or oxy derivatives with N-monosubstituted hydrazines which carry a residue on the N'-nitrogen atom that can be split off by hydrolysis, condensed,

      the open-chain products obtained are treated with hydrolyzing agents and at the same time or subsequently: the pyrazole ring closes.



  The other starting materials are known or can be obtained by processes known per se.



       In the following example the temperatures are given in degrees Celsius.



  <I> Example </I> 15 g of 1-methyl-3-amino-4-cyano-pyrazole are heated to 190-200 for 10 hours with 10 ml of formaride. The deposited precipitate is filtered off and recrystallized from water. This gives 2-methyl-4-aminopyrazolo [3,4-d] pyhmidine of the formula
EMI0002.0093
    The compound melts above 350.



  The starting material is obtained: according to Swiss patent no. 396 011.

 

Claims (1)

Claim process for the preparation of new 2-R-4-R'-6-R "- pyrazolo, [3,4, d] pyrimidines, in which R represents a substituent, R 'represents the NH2 group and R" represents the has the same meaning as R 'or represents hydrogen or a lower alkyl radical, as well as their tautomeric forms and salts; of these compounds, characterized in that 1-R-3-aminopyrazole-4-nitriles are reacted with corresponding functional carboxylic acid derivatives containing the NH2 group. SUBClaims 1. The method according to claim, characterized in that one starts from Canbowäureamiden. 2. The method according to claim and sub-claim 1, characterized in that obtained salts are converted into the free compounds. 3. procedure; according to claim and sub-claim 1, characterized in that free compounds obtained are converted into their salts.