Patent GB-377255-A (GB)
Title: Manufacture of therapeutically active compounds
IPC: C07D473/12
Filed: 1931-04-14
Abstract: Perhydrocarbazole derivatives are prepared by exchanging the imine hydrogen in known manner for a residue containing one or more basic nitrogen atoms, i.e. capable of combining by addition with hydrogen chloride or bromide, said basic nitrogen atom or atoms being linked by an aliphatic residue with the imino group. The same products may also be obtained by treating a compound, derived from perhydrocarbazole by substitution of the imine hydrogen by an aliphatic residue containing a reactive group, with a compound containing a group capable of interaction with the reactive group and containing one or more nitrogen atoms which are either basic in character or rendered basic by subsequent treatment, e.g. reduction. The aliphatic residue may contain oxygen atoms or other nitrogen atoms or cyclic carbon atoms. According to the examples, (1) 1-perhydrocarbazylethylpyridone-2-imide is prepared by treating perhydrocarbazole with ethylene oxide or ethylene chlorhydrin, converting the oxyethylperhydrocarbazole into the N-chlorethyl compound by means of thionyl chloride, and treating it with 2-aminopyridine; using 4-methyl-2-aminopyridine in the final stage, 1-perhydrocarbazylethyl - 4 - methylpyridone - 2 - imide is obtained; similarly, 1-perhydrocarbazylethylpyridone-4-imide is formed by interaction of the N-chlorethyl compound with 4-aminopyridine, 1-perhydrocarbazylethylquinolone-2-imide using 2-aminoquinoline, 1-perhydrocarbazylethyl - 2 - methyl - 6 - ethoxyquinolone-4-imide using 6-ethoxy-4-aminoquinaldine, 1-perhydrocarbazylethylimidazole using imidazole, 1-perhydrocarbazylethyl - 5 - methylpyrazoline using 5-methylpyrazoline, methylaminoethyl-perhydrocarbazole using methylamine, diethyl-aminoethylperhydrocarbazole using diethyl-amine, benzylaminoethylperhydrocarbazole using benzylamine, methylbenzylaminoethyl-perhydrocarbazole using methylbenzylamine and 1-perhydrocarbazyl-2-hydroxy-3-diethyl-aminopropane using diethylaminoepihydrin; (2) 1-(1<1>-perhydrocarbazyl-3<1>-diethylaminopropyl-2<1>) -pyridone-2-imide is obtained by converting 1 - perhydrocarbazyl - 2 - hydroxy - 3 -di-ethylaminopropane into the 2-chloro compound by means of thionyl chloride and treating it with 2-aminopyridine; (3) 8-perhydrocarbazyl-ethoxycaffeine is prepared by interaction of N-oxyethylperhydrocarbazole with chlorocaffeine; from the same starting material is obtained diperhydrocarbazylethane using ethylene bromide, 2-imino-3-perhydrocarbazylethyl-4-methylthiazole-2 : 3-dihydride using 4-methyl-2-aminothiazole, 1 - perhydrocarbazylethyl - 2 - methylimidazole-4 : 5-dihydride using 2-methyl4 : 5-dihydroimidazole and 2-perhydrocarbazyl-ethylaminopyridine using 2-aminopyridine; (4) m-tolylhydrazine is condensed with cyclohexanol, the resulting 7-methyl-1 : 2 : 3 : 4-tetrahydrocarbazole then hydrogenated to 2-methylperhydrocarbazole, which is treated in succession with ehtylene chlorhydrin, thionyl chloride and 2-aminopyridine, to form 1-(2<1>-methyl) perhydrocarbazylethylpyridone-2-imide. The formul  of the products are given.  The Provisional Specification states that the residue connecting the imino group with the basic nitrogen atom or atoms may also be cyclic or alicyclic or may comprise an aliphatic chain containing sulphur atoms.  If the connecting member is to consist wholly or partly of a cyclic hydrocarbon residue, the perhydrocarbazole may be treated with an aromatic body containing nitrogen and a reactive halogen, e.g. p-nitrochlorbenzene and the product further converted into a polyamino compound.