Patent GB-1420067-A (GB)
Title: Aryldiamides
IPC: A61K38/00
Filed: 1972-02-15
Abstract: 1420067 Amides ASTRA LAKEMEDEL AB 15 Feb 1973 [15 Feb 1972] 6943/72 Heading C2C The invention comprises amides of the Formula I  wherein n is 0 or 1; each of R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP>, R<SP>4</SP> and R<SP>5</SP> is H, halogen. C 1-3  alkyl or C 1-3  alkoxy; each of R<SP>6</SP>, R<SP>7</SP>, R<SP>8</SP> and R<SP>9</SP> is H or C 1-3  alkyl; R<SP>10</SP> is H or R<SP>10</SP> and R<SP>9</SP> together with the nitrogen and carbon atoms, to which they are respectively attached, form a 5- or 6-membered saturated heterocyclic ring; each of R<SP>11</SP> and R<SP>12</SP> is H or C 1-3  alkyl; each of R<SP>13</SP> and R<SP>14</SP> is H or C 1-3  alkyl or -N(R<SP>13</SP>)R<SP>14</SP> is a 4-, 5- or 6-membered saturated heterocyclic ring or R<SP>12</SP> and R<SP>14</SP> together with the carbon and nitrogen atoms, to which they are respectively attached, form a 5- or 6- membered R saturated heterocyclic ring, provided that at least one of R<SP>1</SP> to R<SP>5</SP> is alkyl or alkoxy or halogen when n is 0 and R<SP>8</SP>-R<SP>14</SP> are H; and provided that none of R<SP>1</SP> to R<SP>5</SP> are halogen when -N(R<SP>13</SP>)R<SP>14</SP> is a 1-pyrrolidinyl group, their therapeutically acceptable acid addition salts and their preparation. The compounds are prepared by reacting amines of the Formula II with compounds of the Formula III Y.CO.C(R<SP>8</SP>)R<SP>9</SP>.N(R<SP>10</SP>).CO.C(R<SP>11</SP>)R<SP>12</SP>.N(R<SP>13</SP>)R<SP>14</SP> wherein Y is OH, halogen or a phenylsulphonyloxy radical optionally substituted by a C 1-4  alkyl radical, or by reacting compounds of the Formula IV with nitriles of the formula Compounds of the Formula I above in which R<SP>12</SP> and R<SP>14</SP> are not part of a saturated heterocyclic ring may also be prepared by reacting compounds of the Formula VI wherein X is halogen or a phenylsulphonyloxy radical optionally substituted by a C 1-4  alkyl radical with amines of the formula HN(R<SP>13</SP>)R<SP>14</SP>. Compounds of the above Formula I in which R<SP>13</SP> and R<SP>14</SP> are H may be made by reacting compounds of the Formula X with hydrazine hydrate and hydrochloric acid. The resulting compounds may be converted into therapeutically acceptable acid addition salts and/or resolved into their optically active antipodes in the cases where the compounds or salts have at least one asymmetric carbon atom. Compounds of Formula VI above in which X is halogen are obtained by reacting amines of the formula Ar-NH-CO.C(R<SP>8</SP>)R<SP>9</SP>.NH 2  where Ar is a radical of the formula with acid halides of the formula 2-Aminoacetanilide is obtained by reacting ammonia with 2-chloroacetanilide resulting from the reaction between aniline and chloroacetyl chloride. 2-Aminoaceto-2<SP>1</SP>-6<SP>1</SP>-xylidide and its hydrochloride are obtained by reacting ammonia with 2-chloroaceto-2<SP>1</SP>,6<SP>1</SP>-xylidide. 2-Amino-N-(α,α-dimethylbenzyl)acetamide is prepared by reacting ammonia with 2-chloro-N- (α,α-dimethylbenzyl)acetamide, resulting from the reaction between α,α-dimethylbenzylamine hydrobromide and chloroacetyl chloride. 2 - Amino - N - (α,α - dimethylbenyl) propionamide is obtained by reacting ammonia with 2- bromo-N-(α,α-dimethylbenzyl) propionamide, resulting from the reaction between α,α-dimethylbenzylamine and 2-bromopropionyl bromide. Compounds of Formula X above are obtained by reacting potassium phthalimide with compounds of Formula VI above. Pharmaceutical compositions, suitable for oral or parenteral administration, contain the above novel compounds or therapeutically acceptable acid addition salts thereof in association with pharmaceutically acceptable carriers.