Patent GB-804786-A (GB)
Title: New indole derivatives and process for their preparation
Filed: 1956-12-17
Abstract: The invention comprises indole derivatives of the formula: <FORM:0804786/IV (b)/1> where R and R1 are the same or different and represent hydrogen atoms, lower (1-6C) alkyl or aralkyl groups, X is hydrogen, halogen, lower alkyl or lower alkoxy and B is piperidyl, N-alkylpiperidyl, N-aralkylpiperidyl, or N-alkyl - 1 : 2 : 5 : 6 - tetrahydropyridyl attached to the indole nucleus at the 2- or 4-position of the B nucleus, or corresponding radicals formed by substituting the pyridyl or piperidyl nucleus by lower alkyl; and the salts of the said derivatives.  The invention also comprises the process for making the said compounds by reduction of the corresponding pyridyl compounds or their salts, e.g. by catalytic hydrogenation or the action of alkali metal borohydrides.  In examples, the hydrogenation in presence of Pt in an alcoholic or aqueous alcoholic medium of the 2-pyridyl compound corresponding to the following products is described; the pyridyl compounds being prepared and employed as quaternary methobromide, or bromobenzylate: 2-(1-methyl-2-piperidyl) - 3 - ethylindole, 2 - (1 - benzyl - 2 - piperidyl) - 3 - ethylindole, 2 - (1 - methyl - 2 - piperidyl) - 3 - methylindole, 2 - (1 - methyl - 4 - piperidyl) - 3 - ethylindole, 2 - (1 - ethyl - 2 - piperidyl) - 3 - methylindole, and similar 3 - ethyl, 3 - propyl - and 3 - isopropylindole products, 2 - (2 - piperidyl) - 3 - ethyl - 5 - methoxyindole, 2 - (1 - methyl - 2 - piperidyl) - 3 - ethyl - 5 - chloroindole, similar 6 - chloro - and 6 - methoxyindole products, 2 - (1 : 4 - dimethyl - 2 - piperidyl) - 3 - ethylindole; the reduction with potassium borohydride of the 2-pyridyl compounds corresponding to 2-(1-methyl - 1 : 2 : 5 : 6 - tetrahydro - 2 - pyridyl)-3 - ethylindole and 2 - (1 : 4 - dimethyl - 1 : 2 : 5 : 6 - tetrahydro - 2 - pyridyl) - 3 - ethylindole is described; reduction with sodium in alcohol or catalytic hydrogenation with platinum oxide in acetic acid gives 2-(2-piperidyl) - 3 - ethylindole.  All the products may be converted to hydrochlorides and other salts, e.g. phosphates, nitrates, sulphates, maleates, fumarates, citrates, tartrates, methanesulphonates, ethanedisulphonates, methiodides, methochlorides, methobromides or corresponding ethyl analogues.  Starting materials.-The following quaternary ammonium salts are prepared by treating the corresponding tertiary bases with the appropriate quaternating agents in acetone solution: 2 - (2 - pyridyl) - 3 - ethylindole methobromide and bromobenzylate, 2 - (2 - pyridyl) - 3 - methyl-, -propyl- and -isopropyl-indole methobromides, 2 - (4 - pyridyl) - 3 - ethylindole methobromide, 1 - methyl - 2 - (2 - pyridyl) - 3 - ethylindole methobromide, 2 - (2 - pyridyl) - 3 - ethyl-5- and 6-methoxy- and -chloro-indole methobromides, 2 - (2 - pyridyl) - indole methobromide and 2 - (4 - methyl - 2 - pyridyl) - 3 - ethylindole methobromide.  Reference is also made to the preparation of certain of the tertiary bases by ring closure, by the Fischer reaction, of the appropriate 2-acylpyridine phenylhydrazones, and to the preparation of certain of the corresponding ketones as follows: 2 - valerylpyridine from 2 - cyanopyridine and butylmagnesium bromide; 2 - isovaleryl-pyridine from 2-cyanopyridine and isobutyl-magnesium bromide; (4-methyl-2-pyridyl)-propyl ketone from 2-cyano-4-methylpyridine and n-propylmagnesium bromide. 1-Methyl-2-(2-pyridil) - 3 - ethylindole is prepared by the action of methyl iodide on the sodium derivative of 2-(2-pyridyl)-3-ethylindole in liquid ammonia.