Patent GB-835918-A (GB)
Title: Manufacture of alkylated pyrazolopyrimidines
IPC: C07D487/04
Filed: 1957-02-11
Abstract: The invention comprises 4- and/or 6-oxo-hydro - pyrazolo - (3:4 - d) pyrimidines (incluing the tautomeric 4- and/or 6-hydroxypyrazolo - (3:4 - d) pyrimidines) having the nucleus <FORM:0835918/IV (b)/1> being unsubstituted in the 3-position but being alkylated at at least one ring nitrogen atom and optionally bearing at either of the 4- or 6-positions not carrying an oxo group, a free or alkyl substituted hydroxyl, mercapto or amino group, and salts thereof. The compounds are made by reacting a 3-aminopyrazole-4-carboxylic acid ester, amide or nitrile and a formic or carbonic acid functional derivative, e.g. formamide, urea, thiourea, guanidine, a chloroformic ester or phosgene, the functional derivatives being so chosen that at least one of the functionally converted carboxylic groups contains nitrogen.  The starting materials may be so chosen as to give the desired final products directly or alternatively an intermediate product lacking the N-alkyl and/or 4- or 6- oxo groups, which is converted to the desired product for example by alkylation or by converting a free or alkylated mercapto group in the 4- or 6-positions to an oxo group by hydrolysis.  Preferred products comprise compounds which are alkylated at at least two ring nitrogen atoms by alkyl groups of 1-6 carbon atoms, e.g. methyl, specified products being 2:5-dimethyl-, 2:7-dimethyl-, 5:7 - dimethyl -, 2:5:7 - trimethyl - and 1-isopropyl - 5:7 - dimethyl -, 4:6 - dioxo-4:5:6:7 - tetrahydro - pyrazolo - pyrimidine; 1:5 - dimethyl -, 2:5 - dimethyl - 6 - methyl-mercapto -, 2:5 - dimethyl - 6 - amino - and 1-isopropyl - 5 - methyl -, 4 - oxo - 4:5 - dihydro-pyrazolo - pyrimidine; 2:7 - dimethyl - 4-amino - and 2:7 - dimethyl - 4 - methylmercapto -, 6 - oxo - 6:7 - dihydro - pyrazolo-pyrimidine and 1 - isopropyl - 4 - hydroxy-and - isopropyl - 4:6 - dihydroxy pyrazolo-pyrimidine.  The products are used pharmaceutically as stimulants and diuretics suitably in the form of salts such as the acid addition salts with hydrohalic, sulphuric, phosphoric, nitric, perchloric and aliphatic, alicyclic, armatic and heterocyclic carboxylic and sulphonic acids including ascorbic acid, methionine, tryptophane, lysine and arginine.  Also, the hydroxy or mercapto derivatives form salts with metals.ALSO:Pharmaceutical preparations having diuretic or caffeine-like stimulant action comprise 4-and/or 6 - oxo - hydro - pyrazolo - (3:4 - d)-pyrimidines having the nucleus <FORM:0835918/VI/1> being unsubstituted in the 3-position, but being alkylated on at least one ring nitrogen atom and optionally bearing at either of the 4- or 6-positions not carrying an oxo group, a free or alkyl substituted hydroxyl, mercapto or amino group, or salts thereof in admixture with a pharmaceutical organic or inorganic carrier suitable for enteral, parenteral or topical administration. The preparations may take the form of tablets, dragees, solutions, suspensions or emulsions specified diluents being gelatine, lactose, starches, magnesium stearate, talc, vegetable oils, benzyl alcohols, gums, polyalkylene glycols and cholesterol.  3-Amino-pyrazoles used as starting materials bearing a free or functionally converted carboxylic group in the 4-position such as an ester, amide, nitrile or amidine group are made by reacting 2 - cyano - b  - oxo - propionic acid, or a functional derivative thereof, with a hydrazine derivative.  The preparation of 4-carbethoxy -, 2 - isopropyl - 4 - carbamoyl -, 2 - isopropyl - 4 - carbethoxy - and 2 - methyl - 4-carbamoyl -, 3 - amino - pyrazole is described.