Patent GB-1081317-A (GB)
Title: Improvements in or relating to caged amines
IPC: C07C61/125
Filed: 1965-10-21
Abstract: Novel compounds of general formula <FORM:1081317/C2/1> where one symbol R represents amino, (C1-C4) -alkylamino, di-(C1-C4)-alkylamino, (C1-C4) -acylamino, guanidino or ureido and the other three symbols R represent H, or, alternatively, when in the 1, 2 or 11 position, one R may be aminomethyl, (C1-C4) - mono- or di - alkylaminomethy or (C1-C4)-acylaminomethyl, and acid addition salts thereof, are prepared by one of the multistage processes following: 1-Amino compounds may be prepared by first heating compound XIII <FORM:1081317/C2/2> with compound XIV <FORM:1081317/C2/3> to give compound VII <FORM:1081317/C2/4> which is then irradiated with a mercury vapour lamp to give compound V <FORM:1081317/C2/5> (R1=methyl) which on hydrolysis gives V(R1=H).  This acid V is dechlorinated to give acid VI <FORM:1081317/C2/6> which is converted to the isocyanate via the acid chloride and azide and hence to the required amine by hydrolysis.  The hexachloroamine may be similarly prepared from the acid V. 2-Amino compounds may be prepared by first heating compound XV <FORM:1081317/C2/7> (which is prepared by reaction of methyl propiolate and hexachlorocyclopentadiene) with cyclopentadiene to give compound IX <FORM:1081317/C2/8> which on irradiation by a mercury vapour lamp gives compound VIII <FORM:1081317/C2/9> where R1 is methyl, which is converted to the amine as for the 1-amino compounds above. 4-Amino compounds are prepared either by reaction of p-toluene sulphonyl azide and Isodrin XVII <FORM:1081317/C2/100> to give compound XVIII <FORM:1081317/C2/111> which with trifluoro acetic acid gives compound XIX <FORM:1081317/C2/122> which on irradiation with a mercury vapour lamp gives compound XX <FORM:1081317/C2/13> which may be hydrolysed and then dechlorinated to give the required amine, or Isodrin XVII is reacted with t-butoxycarbonyl azide and the product treated with formic acid to give compound XXII <FORM:1081317/C2/14> or passed down an alumina column to give compound XXIV <FORM:1081317/C2/15> which may be hydrolysed to give compound XXV <FORM:1081317/C2/16> and compounds XXII or XXV are hydrolysed to the imine XXIII <FORM:1081317/C2/17> which on fusion with ammonium acetate gives the hexachloroamine III <FORM:1081317/C2/18> which can be dechlorinated to give the desired amine.  11-Amino compounds are prepared by reacting tetrachlorocyclopentadienone cyclic ethylene ketal with 1,2,3,4,7,7-hexachlorobicyclo [2.2.1] hepta-2,5-diene to give compound XXVI <FORM:1081317/C2/19> which is irradiated to give compound XXVII <FORM:1081317/C2/20> whichis dechlorinated and hydrolysed to the ketone XXX <FORM:1081317/C2/210> which is converted to its oxime and the latter reduced to the 11-amine, or alternatively the dechlorination may be carried out at the final stage instead of after compound XXVII, or alternatively the ketone XXX may be prepared by reaction of cyclopentadiene with 1,2,3,4 - tetrachlorobicyclo [2.2.1] hepta-2-5-dien-7-one ketal and irradiation and dechlorination of the resultant product.  Aminomethyl compounds are prepared by treating the above prepared 1- or 2-carboxylic acids with SOCl2 and ammonia and reduction of the amides so formed, or by treatment of the 11-ketone XXX with methoxymethylene triphenylphosphorane to give the 11-methoxymethylene compound which is oxidized to the 11-aldehyde and the latter converted to the aminomethyl compound via the aldoxime. The amines may be alkylated or acylated in the usual manner, or salts may be formed where desired.  Pharmaceutical compositions for oral or subcutaneous administration, and having antiviral activity, comprise a novel compound of the first general formula above and a carrier therefor.