Patent GB-771814-A (GB)
Title: New butyryl amides and processes for their manufacture
IPC: C07D213/38
Filed: 1955-06-03
Abstract: The invention comprises compounds of the formula <FORM:0771814/IV(b)/1> wherein R1 is H, Cl or Br or an alkyl or alkoxy group containing at most 6 carbon atoms and R2 and R3 are dialkylamino (containing not more than 6 carbon atoms), piperidino, morpholino or pyrrolidino groups, and their nontoxic acid addition and quaternary salts; and their preparation by condensing a compound of the formula <FORM:0771814/IV(b)/2> with a 2-halogeno-pyridine and a compound of the formula R3CH2CH2X, where X is a halogen atom, in the presence of a basic condensing agent.  The invention also includes the further step of hydrolysing and decarboxylating the above butyryl amides to form the corresponding propylamines.  The substituted phenyl-acetamide may be condensed with the 2-halogenopyridine and the disubstituted amino-ethyl halide in any order or simultaneously.  Condensing agents mentioned are sodium hydride, lithium amide, potassium amide, lower alkyl Grignard reagents and sodium amide, the latter being preferred. An inert solvent such as toluene, benzene or ether is advantageously used. The hydrolysis and decarboxylation are advantageously performed in the presence of acids such as hydrochloric, sulphuric and trichloracetic acids, or basic media such as aqueous and alcoholic alkali, sodium, potassium and calcium hydroxides; or sodium amide in an inert solvent.  Acid addition and quaternary salts such as hydrochlorides, maleates, tartrates, citrates, methiodides, ethobromides and dimethylsulphates and their preparation are referred to.  In examples: (1) p-chlorophenylacetic acid dimethylamide, prepared from the corresponding acid chloride and dimethylamine, is condensed with 2-bromopyridine to give a -(p-chlorophenyl) - a  - (2 - pyridyl) - acetic acid dimethylamide, which on condensation with b -dimethylaminoethyl chloride yields a -(p-chlorophenyl) - a  - (2 - pyridyl) - g  - dimethylamino - butyric acid dimethylamide.  This is also prepared from a -(p-chlorophenyl)-g -dimethylamino butyric acid dimethylamide and 2-bromopyridine, the former itself being prepared from p-chlorphenylacetic acid dimethylamide and b -dimethylaminoethyl chloride; (2) a  - phenyl - a  - (2 - pyridyl) - g  - dimethylaminobutyric acid dimethylamide is prepared by the first method of example (1); (3) to (12) a -(p-chlorophenyl)-a -(2 - pyridyl) - g  - dimethylaminobutyric acid diethylamide, N - [a (p - bromophenyl) - a  - (2 - pyridyl) - g  - dimethylaminobutyryl] - piperidine, a  - (p - chlorphenyl) - a  - (2 - pyridyl) - g  - pyrrolidino-butyric acid dimethylamide, a -phenyl - a  - (2 - pyridyl) - g  - morpholinobutyric acid dimethylamide, a  - (p - bromophenyl) - a  - (2 - pyridyl) - g  - piperidinobutyric acid diethylamide, N - [a  - (chlorophenyl) - a  - (2 - pyridyl)-g -piperidinobutyryl]-pyrrolidine, a -(o-chlorophenyl) - a  - (2 - pyridyl) - g  - dimethylamino - butyric acid dimethylamide, a -(m-methoxyphenyl) - a  - (2 - pyridyl) - g  - dimethylamino - butyric acid dimethylamide, the corresponding p-methoxy compound and a -(p-methylphenyl)-a  - (2 - pyridyl) - g  - dimethylaminobutyric acid dimethylamide are similarly prepared; the latter is also prepared by condensing p-methylphenylacetic acid dimethylamide with 2-chloropyridine and b -dimethylaminoethyl chloride in one reaction; (13) a -(p-chlorophenyl)-a -(2-pyridyl) - g  - dimethylaminobutyric acid dimethylamide is heated with sulphuric acid or with potassium hydroxide in a solvent mixture to yield 3 - (p - chlorphenyl) - 3 - (21 - pyridyl)-N,N-dimethylpropylamine. The other amides obtained above are similarly converted to the corresponding propylamine derivatives.  Acid addition and quaternary salts of the above amides are also prepared.  Starting materials.  Substituted phenyl acetamides are prepared from the corresponding acid chlorides and the appropriate amine.