BE518622A - - Google Patents

Description

       

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  IMPROVEMENTS TO PYRIMIDINE DERIVATIVES AND METHODS FOR THEIR
PREPARATION.



   The present invention relates to pyrimidine derivatives and to processes for their preparation.



   It has been found that certain 2-dialkylamino-4-amino-5-aryl-6-alkyl pyrimidines have unexpected and useful properties in preventing the growth of certain microorganisms. 2,4-diaminopyrimdidines with unsubstituted diamino groups are in general. growth inhibitors against lactic acid bacteria and Leuconostoc citrovorum and these activities are generally accompanied by inhibitory activities against certain protozoa, in particular plasmodia of experimental malaria, The activity of the new group of substances towards Lactobacillas casei and Leuconostoc citrovorum is greatly reduced,

   but it unexpectedly retains a high degree of antimalarial activity. Other interesting properties of the new group of substances, such as their improved solubility, make them particularly valuable for certain purposes. the compounds of the present invention be represented by the general formula (I) in which R 1 and R are lower alkyl radicals which can unite to form with the N atom a heterocyclic amino radical; R3 is lower alkyl or aralkyl which may be substituted with halogen groups, and X and Y are the same or different and represent hydrogen or halogen atoms.

   The compounds can be prepared by a process analogous to that described in Belgian Patent No. 503,913, that is to say by the reaction of a beta-alkoxy-alpha-phenylacrylonitrile (II) (formula in which R is an alkyl radical lower) with an asymmetric bisubstituted quanidine (III)

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 EMI2.1
 
 EMI2.2
 The present invention therefore covers compounds of general formula (I) in which R and R are lower alkyl radicals which can unite to form with the N atone a heterocyclic amino radical;

   R3 is lower alkyl or aralkyl which may be substituted
 EMI2.3
 by halogen groups and X and Y are the same or different and re-create atoms of hydrogen or halogen.



   The compounds can be presented as acid addition salts which are not toxic at the doses at which they are administered, and all such salts are within the scope of the invention.



   The invention will be described hereinafter with reference to the following examples, in which all temperatures are given in degrees centigrade.
 EMI2.4
 



  EXEMPY 1 ..- 2MimetàY> mino <-anmo-5-D-mhlorDhéWL ± -é% hY> zhnidne. We react to I gr. alpha-propionyl-p-chlorphenyl-acetonitrile with diazcmethane from 15 gr. of nitroscmethylurea, in 1 ether. It is dissolved in 50 ml. of 1- * alpha-p-chlorphérwl-beta-methoxybeta-ethylacrylonitrile ethanol formed and reacted with a solution of N-dimethylguanidine prepared by dissolving 13.6 gr. of its sulfate in 50 ml.
 EMI2.5
 of water and adding a sodium ethoxide solution from 2.3 gr. of sodium dissolved in 60 ml. ethanol. The mixture is heated in a water bath for 6 hours. It is then diluted with water and the precipitate is filtered off.
 EMI2.6
 , -d3anethyLatnino - 5 amino pchlorphéh6-ethypyrimidine.

   After recrystallization from benzene ligroin, it forms needles with a melting point of 130-131. EXEMPY 2. -
 EMI2.7
 2-pentam.éthyieneanïno.-amino 5 u-chlornhé 1-6 - ethrluyrimidine.



  N-pentamethylene guanid3ne hydrobromide, melting at 125a, is prepared by the reaction of piperidine with S-ethylthiouronium bromide in ethanol.



  One reacts 1l gr. alpha p-chlorphêryïrbta-; n.ethoxy bta-ethylacrylonitrile with Nertamethylèxzeguanïdine, obtained from 106 gr. of hydrobromide and 1.15 gr. of sodium in 100 ml. ethanol. The mixture is refluxed overnight and then diluted with 200 ml. water and basified with a NaOH solution. The precipitate of 2-pentamethylene-amino-4 ,, -amino-5-p-chlorphenyl-6-ethylpyrimidine is filtered. It is dissolved in dilute acetic acid. and precipitated with sodium hydroxide solution and finally crystallized from benzene petroleum ether. It has a melting point of 166.

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   The following compounds are prepared in a manner analogous to that already described:
 EMI3.1
 2-dim4thylamino-4..5-p-chlorbenzyl-6-meth, ylpyrimidine mp 259-262P.



  2- (1-morpholino) -4-amino-5-p-chlorphenyl-6-ethylpyr: lmîdine, melting point: 1440 2.-d: tmethylamino-4-amino-5 - (3, 4-dichlorphenyl ) -6-ethylpyrimidine, melting point 2010 ..



  2.-Dimethylamino-4-amino-5- (3, 4-dichlorphenyl) -6-mathylpyrimidine, melting point 157.



   CLAIMS.

** ATTENTION ** end of DESC field can contain start of CLMS **.


    

Claims (1)

Process for the preparation of: - pyrimidine compounds having the general formula EMI3.2 where R1 and R2 are lower alkyl radicals which can unite to form EMI3.3 with the N atom an amino - heterocy-cl radical: Lque- R3 is a lower alkyl or aralkyl group which may be substituted by halogen groups, and X and Y are the same or different and consist of hydrogen atoms or halogen EMI3.4 nes, characterized in that one reacts a beta-alkoxy-.a,! pha phéx'lacxylonitrile having the general formula EMI3.5 or R is a lower alkyl radical with an unsymmetrical bi-substituted guanidine having the general formula: EMI3.6 EMI3.7 -dimethyl7.amino -., 5 p-chlorbenzrl-6-n.etky'lpyrimidine mp 259-2620. from page 3. lines 3 and 4, should be deleted. ** CAUTION ** end of field CLMS may contain start of DESC **.