Patent GB-880804-A (GB)
Title: New 1-substituted pyrazolo-pyrimidines, and process for their manufacture
IPC: C07D487/04
Filed: 1958-11-24
Abstract: The invention comprises pyrazolo-pyrimidines of the formula <FORM:0880804/IV (b)/1> and acid addition salts thereof, wherein R represents a saturated hydrocarbon radical containing at least 4 carbon atoms, e.g. butyl, amyl, cyclopentyl or cyclohexyl, R1 and R2 are amino, mono- or dialkylamino, alkyleneamino, e.g. pyrrolidino- or piperidino- or hydrazino groups or R2 may be hydrogen, and the preparation of these compounds either by reacting an appropriate pyrazolo-[3 : 4-d]-pyrimidine substituted in the 4- and/or 6-position by a halogen atom or a free or etherified mercapto group, with an amine HR1 and/or HR2, or by reacting an appropriate 1-substituted 4-cyano-5-amino pyrazole with formamide.  The products are used pharmaceutically as coronary dilatating agents, preferred compounds being 1-cyclohexyl-, and 1 - sec. - butyl -, 4 - diethylamino - pyrazolo - [3 : 4-d]-pyrimidine.  4 - Halo - or 4, 6 - dihalo - pyrazolo - pyrimidines used as starting materials are prepared by treating the corresponding hydroxy compounds with a halogenating agent such as phosphorus oxychloride, oxybromide, pentachloride or pentabromide.  Mercapto - or alkylmercapto - pyrazolo - pyrimidines used as starting materials are made by reacting the corresponding halogen-compounds with thiourea or a metal mercaptide or mercaptan, or by reacting the corresponding hydroxy-compounds with an agent capable of exchanging oxygen for sulphur such as phosphorus pentasulphide and, if desired, etherifying the resulting thiol groups.  4 - Hydroxy - or 4, 6 - dihydroxy - pyrazolo - pyrimidines are made by condensing a 3-amino-pyrazole-4-carboxylic acid, ester or amide (bearing a substituent R in the 2-position) with formamide or by condensing 2-R-3-amino-4-carbamoyl-pyrazole with urea. 2-R-3-amino-pyrazole-4-carboxylic acid derivatives used in the above process, e.g. 2-cyclohexyl -3-amino-4-carbethoxy pyrazole and the corresponding 2-sec-butyl-, 2-(31-methylbutyl-21)-, 2-pentyl-(31) and 2-cyclopentyl compounds are made by reaction of a hydrazine derivative R-NH-NH2 with an a -cyano-a -formyl acetic ester or its enol ether.  The corresponding 2-R-3-amino-pyrazole-4-carboxylic acids, amides or nitriles are obtained by using the appropriate a -cyano-a -formyl-acetic derivative.  Substituted hydrazines used as starting materials i.e. sec-butyl-, pentyl-(3)-, cyclopentyl and cyclohexyl hydrazine are made by reacting the appropriate ketone with hydrazine and hydrogenating the product.ALSO:Pharmaceutical preparations having a coronary dilatating action and also having an effect on the central nervous system and some diuretic, analgeoic and antirheumatic action comprise pyrazolo-pyrimidines of the formula <FORM:0880804/VI/1> or acid addition salts thereof with organic and inorganic acids, wherein R represents a saturated hydrocarbon radical containing at least 4 carbon atoms, e.g. butyl, amyl, cyclopentyl or cyclohexyl and R1 and R2 are amino, mono- or di-alkylamino, alkyleneamino (e.g. pyrrolidino or piperidino) or hydrazino groups or R2 may also be hydrogen (see Group IV (b)), together with a pharmaceutical carrier suitable for enteral, parenteral or local administration.  The preparations suitably take the form of tablets, dragees, solutions, suspensions or emulsions and may contain preserving, stabilizing, wetting or emulsifying agents.