Patent GB-998284-A (GB)
Title: Improvements in or relating to process for the preparation of pteridine derivatives and novel products
IPC: C07D475/10
Filed: 1962-09-04
Abstract: The invention comprises a substituted pteridine of the general formula <FORM:0998284/C2/1> wherein R represents hydrogen or a lower alkyl, phenyl, thienyl, carbamoyl, amino, mono-lower alkylamino or di-lower alkylamino group, R1 represents a lower alkyl, phenyl, thienyl or amino group, and R3 represents a lower alkyl, halogenated lower alkyl, cycloalkyl, a ,b -lower alkenyl, phenyl-a ,b -lower alkenyl, lower alkenylalkylene, cycloalkenylalkylene, phenyl-lower alkenylalkylene, lower alkynylalkylene, phenyl-lower alkynylalkylene, benzyl or b -phenethyl group, and non-toxic pharmaceutically acceptable acid addition salts thereof, and a process for preparing a substituted pteridine by cyclizing an optionally 2,4-substituted (preferably 2,4-diamino - substituted) 6 - amino - 5 - cyanomethylaminopyrimidines of the general formula <FORM:0998284/C2/2> wherein R2 represents hydrogen or an organic group selected from lower alkyl, halogenated lower alkyl, cycloalkyl, a ,b -lower alkenyl, cycloalkenyl, phenyl-a ,b -lower alkenyl, a ,b -lower alkynyl, phenyl-a ,b -lower alkynyl, lower alkenylalkylene, cyclo-alkenylalkylene, phenyl-lower alkenylalkylene, lower alkynylalkylene, phenyl - lower alkynylalkylene, phenyl, thienyl, furyl, pyrrolyl, pyrimidyl, pyridyl, quinolyl, thiazolyl, benzyl, b -phenethyl, thenyl and carbamoyl with a basic condensing agent to form an optionally 2,4-disubstituted 7-amino-5,6-dihydropteridine having the formula <FORM:0998284/C2/3> wherein R2 has the above significance and isomerizing when R2 represents an a ,b -unsaturated group or oxidizing when R2 represents an a ,b -unsaturated group or oxidizing when R2 is other than an a ,b -unsaturated group said optionally 2,4-substituted,7,amino-5,6-dihydropteridine to form an optionally 2,4-disubstituted-7-amino-pteridine of the general formula <FORM:0998284/C2/4> wherein R3 corresponds to R2 when R2 is hydrogen, lower alkyl, halogenated lower alkyl, cycloalkyl, cycloalkenyl (other than a ,b -cycloalkenyl) lower alkenylalkylene, cycloalkenylalkylene, phenyl-lower alkenylalkylene, lower alkynylalkylene, phenyl-lower alkynylalkylene, phenyl, thienyl, furyl, pyrrolyl, pyrimidyl, pyridyl, quinolyl, thiazolyl, benzyl, b -phenethyl, thienyl or carbamoyl and, when R2 is an a ,b -lower alkenyl, a ,b -cycloalkenyl, phenyl-a ,b -lower alkenyl, a ,b -lower alkynyl or phenyl-a ,b -lower alkynyl, R3 is lower alkyl, cycloalkyl, phenyl-lower alkyl, a ,b -lower alkenyl or phenyl-a ,b -lower alkenyl.  All groups designated lower contain from 1 to 6 carbon atoms, and the cycloalkyl and cycloalkenyl groups contain 5 or 6 carbon atoms.  In the above process the optionally 2,4 - substituted - 6 - amino - 5 - cyanomethylaminopyrimidine reactant is preferably of the general formula immediately below.  Pyrimidine of the general formula <FORM:0998284/C2/5> wherein R represents hydrogen or a lower alkyl, phenyl, thienyl, carbamoyl, hydroxy, amino, mono-lower alkylamino or di-lower alkylamino group, R1 represents hydrogen or a lower alkyl, phenyl, thienyl or amino group and R2 has the above significance, are prepared by treating a 5,6-diamino-pyrimidine of the general formula <FORM:0998284/C2/6> wherein R and R1 have the above significance, with an aldehyde of the formula R2CHO, wherein R2 has the above and treating the resulting pyrimidine of the general formula <FORM:0998284/C2/7> wherein R, R1 and R2 have the above significance, with a cyano compound of the formula R4CN wherein R4 represents hydrogen or an alkali metal.  The term "lower" has the significance indicated above.  The above pyrimidine may also be prepared in one step by reacting the 5,6-diamino-pyrimidine, the aldehyde of formula R2CHO, the cyanogen compound R4CN and an acid such as a mineral acid or a lower alkanoic acid.  p - Chloro - a  - cyanobenzyl phenylsulphonate is prepared by reacting phenylsulphonyl chloride, potassium cyanide and p-chlorobenzaldehyde; by reacting the product with 2,4,5,6-tetra-amino-pyrimidine there is prepared 2,4,6-triamino - 5 - (p - chloro - a  - cyanobenzylamino) - pyrimidine.  2,5,6 - Triamino - 4 - carbamoylpyrimidine is prepared by reacting 2,6-dichloro-5-nitro-4-pyrimidine carboxylic acid methyl ester with ammonia and hydrogenating the resulting 2,6-diamino - 4 - carbamoyl - 5 - nitropyrimidine.  Pharmaceutical compositions contain as the active ingredient a pteridine of the first general formula above. The active compounds are useful as diuretics and hypertensive agents.