GB859287A - Triazolopyrimidine derivatives and their preparation - Google Patents

Abstract

The invention comprises compounds having in one tautomeric form the general formula: <FORM:0859287/IV(b)/1> and their acid addition salts, (wherein R1, R2 and R3, which may be alike or unlike, are hydrogen atoms, alkyl radicals optionally substituted by hydroxy or alkoxy radicals or halogen atoms, or alkenyl or cycloalkyl radicals; R1 and R2, which may be alike or unlike, are amino or mono-or di-alkylamino radicals; R1 is a phenyl or alkylthio radical; R2 is an alkoxy radical or halogen atom; R3 is a halogen atom; or R2 and R3 may jointly form a polymethylene radical); and the preparation thereof by: (1) reacting a compound of the general formula: <FORM:0859287/IV(b)/2> with cyanogen halide, except when R1 and R2 are amino or mono-or di-alkylamino radicals; (2) when one of R1 and R2 is an amino or monoor di-alkylamino radical, reacting a compound of the general formula: <FORM:0859287/IV(b)/3> (wherein one of R4 and R5 is an alkylthio radica or a halogen atom and the other is a hydrogen atom or alkyl radical) with ammonia or a monoor di-alkylamine at an elevated temperature and pressure; (3) cyclising a compound of the general formula: <FORM:0859287/IV(b)/4> (wherein R6 and R7 are alkyl radicals or hydroge atoms; and R8 is -CONH2, -CSNH2, or -C(NH), S. Alk. (in the form of an acid addition salt) wherein alk is an alkyl radical) by heating with a phosphorus oxyhalide in the case where R8 is -CONH2, and by heating with a desulphurising agent in the case where R8 is -CSNH2 or -C(NH). S. Alk (in the form of an acid addition salt), (4) heating a compound of the general formula: <FORM:0859287/IV(b)/5> (wherein R1 and R11 are alkyl radicals) with a compound of the general formula X-C(NH)-NYZ (wherein X is an amino radical or a lower alkylthio radical; and Y and Z are hydrogen atoms or lower alkyl radicals), preferably in the form of an acid addition salt thereof; (5) when R3 is an alkyl radical, optionally substituted by hydroxyl radicals or halogen atoms, adding hydrogen or halogen atoms or hydroxyl radicals respectively to the corresponding compound wherein R3 is an alkenyl radical; and (6) reacting a compound of the general formula: <FORM:0859287/IV(b)/6> with ammonia. 2-Ethyl-4-methyl-6-hydrazinopyrimidine is made from 2-ethyl-4-methyl-6-chloropyrimidine and hydrazine hydrate. Similarly made is 2-n-propyl-4-methyl-6-hydrazinopyrimidine. 2-n-Propyl-4-methyl-6-chloropyrimidine is made by treating 2-n-propyl-4-methyl-6-hydroxypyrimidine with phosphorus oxychloride. Similarly made is 2-ethyl-4-methyl-6-chloropyrimidine. 4 - Methyl - 2 - n - propyl - 6 - (11 - semicarbazido)- pyrimidine is made by reacting 6-hydrazino-4-methyl-2-n-propylpyrimidine with sodium cyanate in the presence of hydrochloric acid. Similarly made is 4-chloro-2-methyl-6-(11-semicarbazido)-pyrimidine. 4-Methyl-2-n-propyl-6-(11-thiosemi-carbazido)-pyrimidine is made by reacting 6-hydrazino-4-methyl-2-n-propylpyrimidine hydrochloride with ammonium thiocyanate. 6 - (11 - S - Ethyl - isothiosemicarbziado) - 4 - methyl - 2 - n - propylpyrimidine hydriodide is made from 6-(11-thiosemicarbazido)-4-methyl-2-n-propylpyrimidine and ethyl iodide.ALSO:Pharmaceutical compositions comprise one or more compounds having in one tautomeric form the general formula: <FORM:0859287/VI/1> and their acid addition salts (wherein R 1, R2 and R 3, which may be alike or unlike, are hydrogen atoms or alkyl radicals, optionally substituted by hydroxy or alkoxy radicals or halogen atoms, or alkenyl or cycloalkyl radicals; R 1 and R2, which may be alike or unlike, are amino or mono- or di-alkylamino radicals. R 1 is phenyl or alkylthio radical, R2 is an alkoxy radical or halogen atom; R 3 is halogen atom; or R2 and R 3 may jointly form a polymethylene radical) in admixture with a non-toxic pharmaceutical carrier or diluent. They may be as solid or liquid compositions, and have a variety of therapeutic properties.