Patent GB-1068655-A (GB)
Title: Pentacyclo-alkane amines and derivatives thereof
IPC: C07C45/63
Filed: 1966-03-23
Abstract: The invention comprises compounds of formulae <FORM:1068655/C2/1> <FORM:1068655/C2/2> <FORM:1068655/C2/3> wherein one of A and one of B represents -(alk)nNRR1 and the others are hydrogen, alk is methylene, isopropylidene or -(CHR2)-, n is O or 1, R is hydrogen or C1- 5 alkyl, R1 hydrogen, C1- 5 alkyl, C1- 7 acyl, or, whe n is O and R is hydrogen, carbamoyl, guanyl or -COOR3, R2 is C1- 4 alkyl and R3 is C1- 5 alkyl or C7- 9 aralkyl, and non-toxic acid addition salts thereof.  Compounds of Formula I are prepared by (i) degrading the corresponding pentacyclo-octane-1-carboxylic acid by successive conversion to its acid chloride, azide and isocyanate, and subjecting the isocyanate either (a) to hydrolysis, to form a primary amine, (b) to reaction with an alcohol to form a compound wherein R1 is COOR3, or (c) to reaction with methanol, followed by lithium aluminium hydride, to form a methylamine; (ii) reacting the above acid chloride with ammonia to form an amide, and reducing this to the aminomethyl compound with lithium aluminium hydride, followed by optional N-substitution, (iii) treating the above acid with an alkyl lithium to obtain the corresponding ketone, coverting this to its oxime and reducing this to the amine, (iv) reacting the above acid chloride with a Grignard reagent to form an a ,a -dimethylmethanol, performing a Ritter reaction with acetonitrile and sulphuric acid to form N-acetyl-a ,a -dimethyl methylamine and hydrolysing off the acetyl group, or (v) subjecting any of the above amine products to alkylation, acylation, reaction with potassium cyanate to form a urea or reaction with S-methyl-isothiourea sulphate to form a guanidine. 3-Amino-pentacyclononanes of Formula II are prepared by brominating 2-cyclpentenone to form successively 2 - bromo - 2 - cyclopentenone and 2,4 - dibromo-2-cyclopentenone, converting the latter by a Diels-Alder reaction with cyclopentadiene to 2 - bromo - 3a,4,7,7a - tetrahydro - 4,7 - methanoinden-1-one, converting this to a 3-bromo-pentacyclodecan-4-one, by irradiation with ultraviolet light, heating this with potassium hydroxide to obtain a 3-carboxy-pentacyclononane, and subjecting this to the treatments described in (1) above. 4-Amino-pentacyclononanes of Formula II are prepared by treatment of 3,5,9,10-tetrachloro-4-pentacyclodecan-4-one with a strong base to form the 3,8,9-trichloro-4-carboxy-pentacyclononane, and dehalogenating by treatment with lithium in o-t-butanol either before or after degradation of the acid as in (I) above, followed by optional N - substitution.  6 - Amino pentacyclononanes of Formula II are prepared by successive 2-bromination and ketalization of dicyclopentadiene-1,8-dione, irradiation of the bromoketal with ultra-violet light to form the 3-bromo-4-keto-pentacyclodecane-7-ketal, treatment of this with a strong base to form the 3-carboxypentacyclononane-6-ketal, decarboxylation and hydrolysis of this to form the 7-keto-pentacyclononane, and either (a) conversion of this to its oxime and reduction of this to the primary amine or (b) reaction of the ketone with methoxymethylene triphenylphosphorane to form the 6-methoxymethylene compound, treatment of this with a strong acid to form the 6-aldehyde, oxidation of this to the 6-carboxylic acid, and treatment of this as in (1) above. 1-Aminopentacyclodecanes of Formula III are prepared by irradiating methyl dicyclopentadiene-5 or 6-carboxylate with ultra-violet light to form a 1-methoxycarbonyl-pentacyclodecane, and subjecting this to hydrolysis and treatment as in (1) above. 3-Amino-pentacyclodecanes of Formula III are prepared in analogous manner to the 1 - amino - pentacyclodecanes.  4 - Aminopentacyclodecanes are prepared by conversion of the pentacyclodecan-4-one (a) to its oxime, which is then reduced to the primary amine, or (b) to the corresponding carboxylic acid, followed by treatment as in (1) above.  The compounds of the invention have antiviral activity and may be administered orally or parenterally in aqueous solutions.