Patent GB-1358721-A (GB)
Title: Tetrahydronaphthyloxyaminopropanols and related compounds
IPC: A61K31/135
Filed: 1971-06-18
Abstract: 1358721 Tetrahydronaphthyloxyaminopropanols and derivatives E R SQUIBB & SONS Inc 18 June 1971 [22 June 1970] 28733/71 Heading C2C Novel compounds of Formula I and stereoisomers of such compounds wherein both of Z and Z<SP>1</SP> are hydroxy or OR<SP>11</SP> or one is hydroxy or OR<SP>11</SP> and the other is hydrogen, or Z and Z<SP>1</SP> together represent oxygen (>O), R<SP>11</SP> is an acyl groap, the radical is a basic nitrogen containing radical of up to 18 carbon atoms wherein R<SP>1</SP> and R<SP>2</SP> are the same or different and are hydrogen, lower alkyl, lower alkenyl, hydroxy-lower alkyl or phenyl-lower alkyl or R<SP>1</SP> and R<SP>2</SP> together with the nitrogen atom from a 5- or 6-membered heterocyclic radical which contains not more than one hetero atom in addition to the nitrogen atom and may be substituted R<SP>3</SP>, R<SP>4</SP>, R<SP>5</SP>, R<SP>6</SP> and R<SP>7</SP> are the same or different and are hydrogen or lower alkyl and R<SP>8</SP>, R<SP>9</SP> and R<SP>10</SP> are the same or different and are hydrogen, lower alkyl monocyclic aryl lower alkyl, lower alkoxy, carboxy or monocyclic cycloalkyl (the terms "lower alkyl" and "lower alkoxy" as empl oyed herein include both straight and branched chain radicals of up to and including eight carbon atoms) and salts thereof are prepared by one of the following reaction sequences ; (a) a naphthol of Formula III is reduced with an alkali metal in NH 3/12  to give a dihydronaphthol of Formula IV which is reacted with an epoxide of Formula V wherein Y is Cl or Br to give a compound of Formula VI which is reacted with a per acid to give a compound of Formula VII which is reacted with the amine R<SP>1</SP>HNR<SP>2</SP> to give a compound of Formula VIII i.e. I Z<SP>1</SP> and Z<SP>2</SP> are O which may optionally be reduced to the 6- or 7- hydroxy compound and this may optionally be o-acylated in the ring; or (b) a compound of Formula II obtained as in Patent Specification 1,290,881 is reacted with diborane or a lower alkyl borane followed by working up to give a compound of Formula I wherein one of Z<SP>1</SP> and Z<SP>2</SP> is H; or (c) a compound of either Formula XI or XII is dehydrogenated to the naphthols XIII and XIV which is reduced to a compound of Formula XV or XVI which is further reduced to a naphthalene diol of Formula XVII or XVIII the alkali metal salt of which is reacted with the epoxide of Formula V above followed by reaction with the amine R<SP>1</SP>HNR<SP>2</SP> ; or (d) a naphthol of Formula IV above is converted to its o-acetate which is converted to the trans- or cis-isomers of Formula XXV or XXIX which are reacted with an epoxide of Formula V above followed by reaction with the amine R<SP>1</SP>HR<SP>2</SP>; (e) a naphthol of Formula III above is reacted with a per acid to give a compound of Formula XXX which is converted to the trans compound of Formula XXV above followed by further conversion as in (d) above; (f) a compound of Formula I where Z<SP>1</SP> and Z<SP>2</SP> are acyloxy or H is obtained either by forming a compound of Formula XXXIII wherein one of Z<SP>1</SP> or Z is H and the other is OH and R<SP>12</SP> is lower alkyl, monocyclic aryl or lower alkyl monocyclic aryl by reaction with an aldehyde R<SP>12</SP>CHO followed by acylation and acidic hydrolysis or by reaction with phosgene to give a compound of Formulae XXXIVa wherein one of Q or Q<SP>1</SP> is acyloxy and the other is H followed by acidic hydrolysis. Pharmaceutical compositions in conventional forms for oral or parenteral administration and having antifibrillatory activity comprise an above novel compound and a carrier or diluent.