Patent GB-1017973-A (GB)
Title: 8-azasteroids
Inventor: CLARKSON RICHARD
IPC: C07D455/03
Filed: 1963-05-10
Abstract: The invention comprises 8-aza-steroids of the formula <FORM:1017973/C2/1> wherein R1 stands for alkyl containing not more than six carbon atoms and R2 stands for a hydrogen atom or an alkyl, alkenyl or alkynyl radical containing up to six carbon atoms, and acid addition salts thereof, and the preparation thereof by hydrolysis, preferably using an inorganic or organic acid, e.g. hydrochloric acid or oxalic acid, of a compound of the formula <FORM:1017973/C2/2> wherein R1 and R2 have the above meanings and R3 stands for an alkoxy or aralkoxy radical containing up to 12 carbon atoms, conveniently in a diluent or solvent, for example water, and in an inert atmosphere, for example nitrogen. <FORM:1017973/C2/3> The 8-aza-steroids of the last general formula above may be prepared as follows:-The compounds of the Formula (VI) may be obtained by the interaction of the compounds of the Formula (IV) with an alkyl lithium of the formula R5.Li or an alkyl magnesium halide of the formula R5.Mg.X, where R5 stands for a lower alkyl radical and X stands for a halogen atom, for example the iodine atom. Alternatively, those of the compounds of the Formula (VI) wherein R5 stands for a lower alkyl radical of more than one carbon atom may be obtained by the interaction of the compounds of the Formula (IV) with an alkali metal alkynide, for example sodium acetylide, in dimethylsulphoxide, to afford the compounds of the Formula (V), wherein R4 stands for a lower alkynyl radical, followed by catalytic hydrogenation, for example hydrogenation using a palladium-on-charcoal catalyst, of the latter compounds. Those of the compounds of the Formula (II) wherein R2 stands for a lower alkyl radical may be obtained by the interaction of the compounds of the Formula (VI) with an alkali metal, for example lithium, and liquid ammonia and a proton source, for example an alcohol, for example t.-butanol, in a solvent, for example tetrahydrofuran, ether or dioxan.  The compounds of the Formula (VII) may be obtained by the interaction of the compounds of the Formula (III) or (IV) with an alkali metal borohydride, for example sodium borohydride, in a solvent, for example methanol.  The compounds of the formula (VIII), i.e. those of the compounds of the Formula (II) wherein R2 stands for hydrogen, may be obtained by the reduction of the compounds of the Formula (IV) or (VII) by the procedure described above for the conversion of the compounds of the Formula (VI) into those of the Formula (II) wherein R2 stands for a lower alkyl radical.  The compounds of the Formula (IX) may be obtained by Oppenauer oxidation of the compounds of the Formula (VIII).  Those of the compounds of the Formula (II) wherein R2 stands for a lower alkenyl radical may be obtained by the interaction of the compounds of the Formula (IX) with a lower alkenyl magnesium halide, and those of the compounds of the Formula (II) wherein R2 stands for a lower alkynyl radical may be obtained by the interaction of the compounds of the Formula (IX) with an alkali metal lower alkynide in dimethylsulphoxide.  Therapeutic compositions having progestational, androgenic and anabolic properties for oral or parenteral administration, e.g. as tablets, capsules, solutions, suspensions, emulsions or dispersable powders, comprise the compound of the first general formula above and a pharmaceutically acceptable diluent or carrier, optionally with the addition of cod liver oil or an additional known medicinal steroid.