CH473800A - Process for the preparation of new heterocyclic derivatives - Google Patents

Description

  

  Process for the preparation of novel heterocyclic derivatives The present invention relates to a process for the preparation of novel heterocyclic derivatives which have f-adrenergic blocking activity and which are therefore used in the treatment or prophylaxis of heart diseases such as e.g.

   B. cardiac arrhythmias and angina pectoris, are useful and the formula:
EMI0001.0011
    correspond, where R2 is an alkyl, hydroxyalkyl,

          Cycloalkyl or aralkyl radical with not more than 10 carbon atoms or an alkenyl radical with not more than 6 carbon atoms and the ring B can optionally carry one or more halogen substituents, as well as the salts thereof.



  It is understood that the above definition encompasses all possible stereoisomeric forms of the heterocyclic derivatives in question. These can be optically active forms, or they can be racemates of the diestereameres which are able to exist when there is more than one asymmetric center in the molecule. It is also understood that expressions in which no substituents are mentioned in this description

      z. B. the term alkyl radical, include only the unsubstituted radicals in question.



  A suitable meaning of R2 when it denotes an alkyl radical with not more than 10 carbon atoms is, for example, n-propyl, isopropyl, isobutyl, sec. Butyl, tert-butyl, 1-methylbutyl or 1-methyloctyl radical called.

   A suitable meaning of R2 when it denotes a hydroxyalkyl radical with not more than 10 carbon atoms is, for example, the 2-hydroxy-1,1-dimethylethyl radical. The 1-methyl-3-phenylpropyl radical may be mentioned as a suitable meaning of R2 when it denotes an aralkyl radical having not more than 10 carbon atoms.

    A suitable meaning of R2 when it denotes a cycloalkyl radical having not more than 10 carbon atoms is, for example, the cyclopentyl radical. A suitable meaning of R2 when it denotes an alkenyl radical having not more than 6 carbon atoms is, for example, the allyl radical.



  One or more chlorine or bromine atoms, for example, may be mentioned as suitable halogen substituents which may be present in ring B.



  Particularly valuable heterocyclic derivatives obtainable according to the invention are, for example, 4- (2-Hydroxy-3-isopropylaminopropoxy) -xanthene and 4- [2-Hydroxy-3- (2-hydroxy-1,1-dimethylanuno) propoxy] - xanthene and the salts thereof.



  Suitable salts of the heterocyclic derivatives produced according to the invention are acid addition salts, for example salts derived from inorganic acids, e.g. B. hydrochlorides, hydrobromides, phosphates or sulfates, or salts derived from organic acids, e.g. B. oxalates, lactates, tartrates, acetates, salicylates or citrates mentioned.



  The process according to the invention is characterized in that a compound of the formula:
EMI0001.0098
         with an alkali metal, e.g. B. sodium, together with a lower alkanol, e.g. B. ethanol, reduced.

        The compounds of formula used as starting material in the above process
EMI0002.0005
    can be obtained as described in British Patent Specification No. 10,58 822 by using a compound of the formula
EMI0002.0008
    with an amine of the formula R2NH2, where Y is the group -CHOH-CH2X or
EMI0002.0012
    represents wherein X represents a halogen atom.



  In the following examples, the parts are given by weight.



  <I> Example 1 </I> One part of 4- (2-hydroxy-3-isopropylaminopropoxy) - xanthone is dissolved in 20 parts of ethanol, and the solution is stirred while 2.5 parts of sodium are slowly added in small pieces for 30 Minutes to be added. The resulting mixture is refluxed for one hour and is then cooled and poured into 200 parts of ice-cold water.

   The mixture thus obtained is extracted with 150 parts of ether in 3 equal portions. The combined ethereal extracts are washed with 100 parts of water in two equal portions and are then dried over anhydrous sodium sulfate and evaporated to dryness. The solid residue obtained in this way is crystallized from cyclohexane. In this way 4- (2-hydroxy 3-isopropylaminopropoxy) -xanthene with a melting point of 128-129 ° C. is obtained.



  The 4- (2-hydroxy-3-isopropylaminopropoxy) xanthone with a melting point of 145-146 ° C. used as a starting point can be obtained as described in Example 5 of British patent specification No. 1058 822.

      <I> Example 2 </I> Example 1 is repeated with the exception that 1 part of 4- [2-hydroxy-3- (2-hydroxy-1,1-dimethylethylamine.o) propoxy] xanthone is used instead 1 part of 4- (2r-hydroxy-3-isopropylaminopropoxy) xanthone is used and 40 parts of ethanol are used instead of 20 parts of ethanol.

   In this way, 4- [2-hydroxy-3- (2 hydroxy-1,1-dimethylethylamino) -propoe-xanthene is obtained, which is crystallized from a mixture of benzene and light petroleum (boiling range 60-80 C) and a Has a melting point of 126 C.



  The 4- [2-hydroxy 3- (2-hydroxy-1,1- @ dimethylethylamino) propoxy] xanthone with a melting point of 128-129 ° C. can be prepared as in Example 10 of British Patent No. <B > 1058 </B> 822 described ..

 

Claims (1)

PATENT CLAIM Process for the preparation of new heterocyclic derivatives of the formula: EMI0002.0068 where R2 is an alkyl, hydroxyalkyl, cycloalkyl or aralkyl radical with not more than 10 carbon atoms or an alkenyl radical with not more than 6 carbon atoms and the ring B can optionally carry one or more halogen substituents, as well as the salts thereof, characterized in that you get a compound of the formula: EMI0002.0081 reduced with an alkali metal together with a lower alkanol. SUBCLAIM Method according to claim, characterized in that sodium is used as the alkali metal. <I> Note from the </I> Federal <I> Office for Intellectual Property: </I> If parts of the description are inconsistent with the definition of the invention given in the claim, it should be remembered that according to Art. 51 of the Patent Act, the claim is decisive for the material scope of the patent.