Patent GB-1301134-A (GB)
Title: SUBSTITUTED 1-PHENYL-2-ALLYLAMINO-ALKANOLS, 1-PHENYL-2-ALLYLAMINO-ALKANES AND alpha-AMINOALKYLPHENYL KETONES
Inventor: COX DAVID ALEXANDER
IPC: C07C275/34
Filed: 1970-07-18
Abstract: 1301134 Diphenylalkyl amines and related compounds PFIZER Ltd 15 July 1971 [18 July 1970] 34931/70 Heading C2C Novel compounds of the general Formula I: wherein R and R<SP>1</SP> each are hydrogen or hydroxy, at least one being hydroxyl; R<SP>2</SP> is hydrogen, halogen or C 1-4  alkyl or alkoxy, R<SP>3</SP> is acylamino, R<SP>11</SP>R<SP>12</SP>N, where R<SP>11</SP> is an acyl group from a carboxylic or sulphonic acid and R<SP>12</SP> is hydrogen or C 1-4  alkyl or R<SP>11</SP> and R<SP>12</SP> together with the nitrogen atom form a cyclic imido group, a C 1-4  alkoxycarbonylamino, a carbamoyl CONR<SP>9</SP>R<SP>10</SP>, a sulphamoyl SO 2 NR<SP>9</SP>R<SP>10</SP> wherein R<SP>9</SP> and R<SP>10</SP> are each hydrogen, C 1-4  alkyl or aryl or together with the nitrogen atom R<SP>9</SP> and R<SP>10</SP> form a heterocyclic group, or an ureido group optionally substituted with one or more C 1-4  alkyl groups on one or both of the nitrogen atoms, any one of which groups may be separated from the phenyl ring by a methylene or ethylene group; R<SP>4</SP>, R<SP>5</SP> and <SP>R6</SP> are hydrogen or C 1-4  alkyl; X is oxygen, sulphur, imino or a direct link; Y is hydrogen and hydroxy, two hydrogens or an oxygen; and n is 1 to 3 when X is other than a direct link and is 0 to 4 when X is a direct link; the carboxylic acid esters and aldehyde condensation products (formed by condensation of I in which R<SP>6</SP> is hydrogen and Y is hydrogen and hydroxy with an aldehyde R<SP>8</SP>CHO where R<SP>8</SP> is hydrogen or C 1-4  alkyl) and pharmaceutically acceptable acid addition salts may be prepared by (a) reacting an amine III: with a ketone or aldehyde IV: to give a Schiffs base which is hydrogenated to I in which R<SP>6</SP> is hydrogen and Y is hydrogen and hydroxy; (b) reacting a phenacyl halide V: wherein Z is halogen and R<SP>13</SP> and R<SP>14</SP> are hydrogen or PO- where P is an easily hydrogenolysable protecting group, at least one of R<SP>13</SP> and R<SP>14</SP> being PO, with an amine VI: The keto group at Y may be optionally reduced followed by hydrogenolysis to remove the protecting groups to produce I in which R<SP>6</SP> is hydrogen and Y is oxygen or hydrogen and hydroxy; (c) reacting an amine VIII: with a halocompound IX: followed by hydrogenolysis to remove the protecting group to produce compounds I in which Y is two hydrogen atoms, and R<SP>6</SP> is hydrogen. In some cases protective groups are not necessary; (d) forming the first intermediate of (b) in which R<SP>3</SP> is replaced by nitro, optionally reducing the keto group Y, reducing the nitro group to amino, forming an acylamino, C 1-4  alkoxycarbonylamino or ureido directly attached to the ring and finally hydrogenolysis to remove the protective groups. Compounds in which R<SP>6</SP> is C 1-4  alkyl may be formed by standard N- alkylation procedures. Pharmaceutical compositions of the compounds I with the usual excipients are #-adrenergic stimulants for the heart when administered orally or parenterally.