Patent GB-1409551-A (GB)
Title: Cyclopent a indene derivatives
IPC: C07C211/41
Filed: 1972-04-14
Abstract: 1409551 1,2,3,3aα,8,8aα - Hexahydrocyclopent[a]inden-1-yl-amines ALLEN & HANBURYS Ltd 28 March 1973 [14 April 1972] 17222/72 Heading C2C Novel 1,2,3,3aα,8,8aα - hexahydrocyclopent[a]inden-1-yl-amines of the general formula wherein each of R 1  and R 2  a hydrogen atom or a C 1-6  alkyl or arylakyl group or R 1  and R 2 , together with the adjacent carbon atom, form a C 3-6  cycloalkone ring, R 3  is a hydrogen atom or a C 1-6  alkyl group and R 4  is a -NR 5 R 6  group, in which each of R 5  and R 6  is a hydrogen atom, a carbamoyl group, or a C 1-6  alkyl group, optionally substituted by an amino, alkylamino, dialkylamino, hydroxy, aryl or optionally substituted aroyl group, or R 5  and R 6 , together with the adjacent nitrogen atom, form a ring which may additionally contain other heteroatoms, and non-toxic, pharmaceutically acceptable salts and esters thereof are prepared (a) when R 3  is a hydrogen atom, by reductively aminating a ketone of the general formula with a compound of the general formula R 4 H; (b) when R 3  is a hydrogen atom and R 4  is -NH 2  by reducing the oxime of a ketone of the second or third general formula above; (c) when R 3  is a hydrogen atom, by reacting a tosyl ester of the general formula with a compound of the fourth general formula above; (d) when R 5  is a carbamoyl group, by reacting the corresponding compound in which R 5  is a hydrogen atom with sodium cyanate; (e) when each of R 1 , R 2  and R 3  is a hydrogen atom and each of R 5  and R 6  is a methyl group, by reacting the corresponding compound in which each of R 5  and R 6  is a hydrogen atom with formaldehyde and formic acid; (f) when R 3  is a C 1-6  alkyl group, by reacting an imine salt of the general formula wherein Hal is a halogen atom, with a compound of the general formula R 3 Li wherein R 3  is a C 1-6  alkyl group; and (g) when at least one of R 5  and R 6  is an optionally substituted C 1-6  alkyl group, by alkylating (directly or reductively) the corresponding compound in which at least one of R 5  and R 6  is a hydrogen atom; followed optionally by salification or esterification of the product. The oxime starting materials used in process (b) above are prepared by reacting the corresponding 3,8-dihydro- or 3,3a,8,8a-tetrahydrocyclopent[a]inden-1[2H]-one with hydroxylamine hydrochloride. 3,3a,8,8a-Tetrahydrocyclopent[a]inden - 1 [2H] - one is prepared by catalytic hydrogenation of 3,8-dihydrocyclopent[a]- inden - 1[2H] - one. 3,8 - Dihydro - 8,8 - dimethyl - cyclopent[a]inden - 1[2H]one is prepared by reacting 3,8-dihydrocyclopent[a]inden- 1[2H]-one with methyl iodide in the presence of sodium hydride; and the corresponding 8,8-dibenzyl compound is prepared analogously using benzyl bromide. (3,3a,8,8a - Tetrahydrocyclopent[a]inden - 1- [2H]-ylidene) isopropyl methyl ammonium iodide is prepared by reacting 3,3a,8,8a-tetrahydrocyclopent[a]inden-1[2H]-one with isopropylamine and treating the resulting 3,3a,8,8atetrahydro - N - isopropylcyclopent[a]inden- 1[2H]-imine with methyl iodide. 1,2,3,3aα,8,8aα - Hexahydrocyclopent[a]inden- 1#-ol toluene-p-sulphonate ester is prepared by reduction of 3,8-dihydrocyclopent[a]inden-1[2H]- one and reaction of the resulting 1,2,3,3aα,8,8aα- hexahydrocyclopent[a]inden- 1# - ol with p. toluenesulphonyl chloride. Pharmaceutical compositions having analgetic activity comprise, as active ingredient, a 1,2,3,3aα,8,8aα - hexahydrocyclopent[a]inden- 1-yl-amine of the first general formula above or a non-toxic, pharmaceutically acceptable salt or ester thereof, together with an inert pharmaceutical carrier.