Patent GB-1176173-A (GB)
Title: Novel Fluorene Compounds
Inventor: HAYES NORMAN FRANK
IPC: C07C/
Filed: 1966-11-14
Abstract: 1,176,173. Fluorene derivatives. ALLEN & HANBURYS Ltd. 3 Nov., 1967 [14 Nov., 1966], No. 50980/66. Heading C2C. The invention comprises novel fluorene derivatives of the Formula (I) in which R 1  is H or a straight or branched C 1-6  alkyl, X is a carbonyl group or a group Alk which is a straight or branched C 1-5  alkylene, R 2  is -AlkNR 3 R 4  in which Alk is a straight or branched C 1-6  alkylene, and R 3  and R 4 , which may be the same or different, are each H, aryl, straight or branched C 1-6  alkyl optionally substituted by one or two aryl radicals or are each an acyl or aroyl group, or together with the nitrogen atom to which they are attached form a heterocyclic ring containing 3 to 8 atoms, which may contain additional hetero atoms, and which may be substituted by alkyl or hydroxyalkyl groups, Z 1  and Z 2 , which may be the same or different are H, halogen, C 1-6 -alkyl, alkoxy, sulphonamide, trihalogenomethyl, nitro, or hydroxy, with the proviso that when Z and Z 1  are H, X is CH 2  and R 1  is C 2 H 5 , R 2  is not (CH 3 ) 2 N-CH 2 - and when Z 1  and Z 2  are H, X is =C=O and R 1  is H, R 2  is not α-diethylaminoethyl, α- piperidinoethyl, α - dimethylaminopropyl, diethylaminomethyl, diethylaminomethyl, piperidinomethyl or morpholinomethyl and physiologically acceptable salts thereof. The above compounds are prepared by one of the following methods: (a) reacting an amine of the formula R 3 R 4 NH with a compound of the Formula (VI) in which Hal is halogen and, if desired, reducing the carbonyl group in the compound thus obtained to a methylene group; (b) reducing the carbonyl group to a methylene group in a compound of Formula (X) which is obtained by reacting the appropriate fluoren-9-ylamine with a haloamide of the formula R 3 R 4 NCO.Alk.Hal; (c) hydrogenolysis of a compound of the above Formula (I) in which X is CO and R 3  and R 4  are both benzyl; (d) hydrazinolysis of the compounds resulting from the reaction of compounds of the above Formula (VI) with alkali metal salts of phthalide or succinimide; (e) condensing a diamine of the formula with the appropriate 9-bromofluorene, or reductively alkylating the appropriate fluorenone with the above diamine to produce compounds of the above Formula (I) in which X is C 1-6  alkylene, and R 2  is CH 2 NR 3 R 4 , where neither R 3  or R 4  is hydrogen. 2 - [(Fluoren - 9 - yl)amino]acetamide hydrochloride is obtained by hydrolysing 2[(fluoren- 2 - yl)amino]acetonitrile hydrochloride resulting from refluxing fluoren-2-ylamine in acetonitrile with chloroacetonitrile. 2 - (Fluoren - 9 - ylamino) - N,N - dimethylacetamide, 2 - (fluoren - 9 - ylamino) - N,N- dimethylpropionamide, 2 - (fluoren - 9 - ylmino)- N - phenylacetamide and 2 - ( fluoren - 9 - ylamino) - N - cyclohexylacetamide are prepared by fluoren - 9 - ylamine with 2 - chloro - N,N- dimethylacetamide, 2 - chloro - N,N - dimethylpropionamide, 2 - chloro - N - phenylacetamide and 2 - chloro - N - cyclohexylacetamide respectively. N - [2 - (Fluoren - 9 - ylidene)aminoethyl] acetamide and 1 - [2 - (fluoren - 9 - ylidene)- amino] - 2 - (dimethylamino) - ethane are obtained by reacting fluorenone with N-(2- aminoethyl)acetamide and N,N-dimethyl-ethylenediamine respectively. Pharmaceutical compositions, having antidepressant anti-convulsant, anti-inflammatory or analgetic activity, comprise one or more of the above compounds or the physiologically acceptable acid addition salts thereof in association with pharmaceutically acceptable carriers. The compositions are in a form suitable for oral or parenteral administration.