Patent GB-911288-A (GB)
Title: Improvements in or relating to 3-amino-4-phenylpyrazoles and method of preparation
IPC: C07D231/38
Filed: 1960-08-22
Abstract: The invention comprises 3-amino-4-phenyl-pyrazoles of general formula <FORM:0911288/IV (b)/1> wherein R1 represents hydrogen, lower alkyl, halogen, lower alkoxy, lower alkylthio, lower acyl, lower alkylsulphonyl, trifluoromethyl, trifluoromethylthio, trifluoromethylsulphonyl, trifluoromethoxy, sulphamyl, nitro, carboxy, amino, or di-lower-alkylamino; R2 represents the groups and atoms listed for R1 above, but R2 may not be hydrogen; and R1 and R2 taken together may represent a methylenedioxy group, and their non-toxic addition salts, such as hydrochloride, maleate, tartrate, acetate, lactate, bismethylenesalicylate, and benzoate, examples of which are given. "Lower alkyl" or "lower alkoxy" is stated to mean straight or branched aliphatic groups having not more than 6 carbon atoms and preferably not more than 4 carbon atoms.  In the examples there were prepared 3-aminopyrazoles containing as substituents at the 4 position:- 2,6-dichlorophenyl, 2 - methoxy - 5 - chlorophenyl, 3,4-methylenedioxyphenyl, 2 - methyl (and 2-carboxy) phenyl, 3-methoxy (and 3-sulphamyl) phenyl, 4-chloro (4-bromo, and 4-fluoro) phenyl and 4-methylthio (4-trifluoromethyl, 4-acetyl, 4-nitro, 4-methylsulphonyl, 4-trifluoromethylthio, 4-trifluoromethylsulphonyl, 4-trifluoromethoxy, 4-amino, and 4-dimethylamino) phenyl.  The invention also includes a process for the production of compounds of the above general formula, and also for the compound in which R1 and R2 are both hydrogen, by allowing an a -formylphenylacetonitrile of general formula <FORM:0911288/IV (b)/2> wherein R1 and R2 have the significance stated above, or may both be hydrogen, to react with hydrazine in an excess of glacial acetic acid.  a -Formylphenylacetonitriles of the above general formula may be made for example by the process of (1) reducing the correctly substituted benzaldehyde or benzoic acid ethyl ester (obtained by esterifying the corresponding free acid) with lithium aluminium hydride to the correspondingly substituted benzyl alcohol, (2) converting into the correspondingly substituted benzyl chloride by treatment with thionyl chloride, (3) treating with sodium cyanide to yield the correspondingly substituted benzyl cyanide, and (4) treating with ethyl formate in the presence of sodium methoxide to yield the a -formylphenylacetonitrile in which the phenyl ring bears the required substituents.  The examples describe the preparation of a -formylphenylacetonitriles in which the phenyl radical is substituted as in the above examples, and also describe the preparation of the following compounds by the steps (1), (2) and (3) above:- ethyl 4-trifluoromethyl-, 4 - trifluoromethylthio-, 4-trifluoromethylsulphonyl- and 4 - trifluoromethoxybenzoates, 4-methylthio-, 4-trifluoromethyl-, 4-trifluoromethylthio, 4-trifluoromethylsulphonyl-and 4-trifluoromethoxy-benzyl alcohols, -benzyl chlorides and -benzyl cyanides.  The above compounds are muscle relaxants and may be administered preferably in a pharmaceutical form, such as tablets, capsules, powders, suspensions, pills, boluses, injection solutions, syrups or gels.