Patent GB-1006885-A (GB)
Title: Improvements relating to derivatives of adamantane
Inventor: PAULSHOCK MARVIN
Filed: 1963-05-09
Abstract: The invention comprises compounds of the formula <FORM:1006885/C2/1> and salts thereof, wherein A is an amino, alkylideneamino or cyclicamino group of the formula (1) <FORM:1006885/C2/2> wherein R1 and R2 are hydrogen (in the case of R1 only); alkyl of 1-12 carbon atoms; alkyl of 1-4 carbon atoms bearing a halogen (chlorine, bromine, fluorine or iodine, but only chlorine or bromine in the case of R2), hydroxy, C1- 3 alkoxy, amino, methylamine, ethylamine, dimethylamino or diethylamino substituent; hydroxyalkoxyalkyl wherein the alkoxy portion has less than 4 and the alkyl portion less than 5, carbon atoms; phenyl; benzyl; phenethyl; or phenylpropyl; and R2 can also be chlorine, bromine, formyl (unless R1 is hydrogen), carboxymethyl, methoxycarbonylmethyl or ethoxycarbonylmethyl; the groups -NR1R2 having at most 12 carbon atoms; 2) <FORM:1006885/C2/3> wherein R3 is hydrogen, C1- 4 alkyl or phenyl and R4 is hydrogen or C1- 4 alkyl; (3) <FORM:1006885/C2/4> wherein n is 2, 3, 4, 5 or 6; or (4) <FORM:1006885/C2/5> and other groups of the formula given in (3) wherein the polymethylene chain is interrupted by oxygen.  The compounds are prepared by (a) reacting a 1-bromoadamantane with a carboxylic acid amide and hydrolysing the resulting amide to the amine; (b) alkylating 1-aminoadamantane; (c) reacting a 1-N-substituted-aminoadamantane oxide with acetic anhydride and hydrolysing the resulting 1-N-alkylacetamido - adamantane; (d) reducing the corresponding N-acylated 1-aminoadamantane with lithium aluminium hydride; (e) reacting 1-aminoadamantane with an aldehyde or ketone to give an alkylidene or arylidene aminoadamantane; (f) reducing an alkylidene-aminoadamantane with lithium aluminium hydride to an alkylaminoadamantane; (g) reacting a quaternary derivative of 1-aminoadamantane with an alkanolamine to give a tertiary amino adamantane; (h) reacting 1-aminoadamantane or a mono-N-substituted derivative thereof with an alkylene oxide to give a hydroxyalkylaminoadamantane; (i) reacting a 1-halodamantane with a cyclic amide and reducing the product to give a compound wherein A is a polymethylene or oxapolymethylene ring; (j) reacting 1-aminoadamantane with a halogen to give an N-haloaminoadamantane; (k) reacting a 1-haloadamantane with an aminocarboxylic acid or lactam to form an adamantane aminocarboxylic acid, or (l) reducing a hydroxyalkyl-1-aminoadamantane to give a cyclic imidoadamantane. N - Bromo - 1 - 1 - amino - adamantane is made by reacting 1-bromoadamantane with hydrogen cyanide and sulphuric acid to give 1-formylaminoadamantane which is then treated with bromine.  The products may be converted into salts such as the hydrohalides, sulphates, phosphates, acetates, lactates, succinates, propionates, tartrates, citrates and bicarbonates.  1 - N - Methylacetamido - adamantane is made by the action of N-methylacetamide on 1-bromo-adamantane.  1 - Dimethylaminoadamantane - N - oxide is made by oxidizing 1-dimethylaminoadamantane with hydrogen peroxide.  1 - (1 - Adamantyl)pyrrolidine - 2 - one is made by reacting 1-bromo-adamantane with pyrrolidine-2-one.  N - [Adamantanyl - (1)] - caprolactam is made by reaction of 1-bromoadamantane with caprolactam in the presence of silver sulphate. 1-Adamantanol is formed as a by-product.  1-Aminoadamantane is made by reacting 1-bromoadamantane with acetonitrile and hydrolysing the resulting 1-acetamidoadamantane.  Pharmaceutical preparations for treatment of virus infections in man and animals comprise the above compounds of the invention and a carrier.  The preparations suitably take forms adapted to oral or parenteral administration (e.g. tablets, capsules, powders, solutions, suspensions or elixirs) or may be administered as a vapour or spray to the mouth or nasal passages.