Patent GB-1069563-A (GB)
Title: Adamantane and tricyclo[4,3,1,1]undecane derivatives
IPC: C07D295/03
Filed: 1964-08-04
Abstract: The invention comprises adamantane and tricyclo [4.3.1.13.8] undecane derivatives of the formula <FORM:1069563/C2/1> wherein Z is a covalent bond or a methylene group; X and Y, which can be the same or different, each represents a methyl or ethyl group; and R represents an amino group of the formula -NR1R2 or -N = CHR3 wherein R1 represents a hydrogen atom, C2- 6 alkenyl, C2- 6 alkynyl, cyclopropyl, cyclobutyl, cyclopropylmethyl or cyclobutylmethyl radical, or a C1- 6 alkyl group which may be substituted with a hydroxyl, methoxy or ethoxy group or an amino group of the formula -NR4R5 wherein R4 and R5 each represents a hydrogen atom or a C1- 6 alkyl group; R2 may be the same as R1, or together with R1 and the nitrogen atom may form a heterocyclic group of the formula -N(CH2)n in which n is 2 to 6, or may represent a chlorine or bromine atom or the group -CHO, -CH2.COOH, -CH2COOCH3 or -CH2 COOC2H5, with the proviso that when R1 is alkenyl or alkynyl with the multiple bond in the 1-position, then R2 is alkyl which may be substituted as stated above; and R3 is an aliphatic hydrocarbon radical, an aromatic hydrocarbon radical or a heterocyclic radical each of which contains not more than 12 atoms.  The substituted or unsubstituted aminomethyl-adamantanes and - tricycloundecanes are prepared by converting 1-adamantane carboxylic acid and 3 - tricyclo [4.3.1.13.8] undecane carboxylic acid to the corresponding acid chlorides with thionyl chlorine, reacting the acid chlorides with ammonia or appropriate amines to form the corresponding acid amides and reducing the amides with lithium aluminium hydride.  The a  - alkyl - 1 - adamantanemethylamines and a -alkyl - 3 - tricyclo - [4.3.1.13.8] undecanemethylamines are prepared by reacting 1-adamantoyl chloride or 3-tricyclo [4.3.13.8] undecoyl chloride with a dialkyl cadmium to form an adamantyl - (1) alkyl ketone or tricyclo [4.3.1.13.8] undecyl-(3) alkyl ketone, treating the ketone with hydroxylamine to form the corresponding oxime and reducing the oxime with lithium aluminium hydride.  The a ,a -dialkyl-1-adamantanemethylamines and a ,a -dialkyl-3-tricyclo [4.3.1.13.8] undecanemethylamines are prepared by reacting 1-adamantoyl chloride or 3-tricyclo-[4.3.1.13.8] undecoyl chloride with an alkyl Grignard reagent to form the corresponding a ,a  - dialkyl - 1 - adamantanemethanol or a ,a -dialkyl - 3 - tricyclo [4.3.1.13.8] undecanemethanol, reacting the methanol derivative with sulphuric acid and acetonitrile to form the corresponding N-acetyl-a ,a -dialkyl-1-adamantane methylamine or N - acetyl - a ,a  - dialkyl - 3-tricyclo - [4.3.1.13.8] undecanemethylamine which is then hydrolysed.  Some substituted amino compounds may be made by other routes.  For example, 1-(aminomethyl) adamantane and 3-(aminomethyl) tricyclo [4.3.1.13.8] undecane may be treated with ethylene oxide or ethylene chloro- or bromo-hydrin to form hydroxyethyl- and bis-hydroxyethyl compounds; with an alkyl chloroacetate and a base to form N-carbalkoxy compounds; with aminoalkyl halides to form N-aminoalkyl compounds; with alkyl halides to form N-alkyl- and N,N-dialkyl-compounds; with sodium hypochlorite or sodium hypobromite to form N-halogen compounds; with formic acid or butyl formate to form N-formamido compounds; and with alkoxyalkyl halides to form N-alkoxyalkyl compounds.  The alkylidene, arylidene or heterocyclicylidene aminomethyladamantanes and aminomethyl-tricycloundecandes are prepared by reacting 1 - (aminomethyl)adamantene or 3 - (aminomethyl) tricyclo [4.3.1.13.8] undecane with appropriate aldehydes.  Pharmaceutical compositions, having antiviral activity, for oral or parenteral administration, comprise a compound of the invention together with a pharmaceutical carrier.  The compositions may be in the form of an animal feedstuff.