Patent GB-1514571-A (GB)
Title: 2,6-methano-benzazocines
IPC: C07D453/06
Filed: 1975-05-19
Abstract: 1514571 1,2,3,4,5,6 - Hexahydro - 2,6 - methano-3-benzazocines STERLING DRUG Inc 19 May 1975 [20 May 1974 12 May 1975] 21272/75 Heading C2C Novel 1,2,3,4,5,6 - hexahydro - 2,6 - methano- 3-benzazocines of the general Formula I R 1  is hydrogen, C 1-7 -alkyl, C 3-7 -alkenyl, C 3-7 - alkynyl, halo-C 3-7 -alkenyl, cycloalkyl, cycloalkyl-C 1-7 -alkyl, 2- or 3-furylmethyl, or 2- or 3-furylmethyl substituted on the unsubstituted, ring carbon atoms by from one to three methyl groups, phenyl-C 1-7 -alkyl, or phenyl-C 1-7 -alkyl substituted in the phenyl ring by from one to two radicals selected from halogen, C 1-7 -alkyl, hydroxy, C 1-4  alkanoyloxy, C 1-7  alkoxy, C 1-7  alkylmercapto, trifluoromethyl, amino and C 1-4 -alkanoylamino or a single methylenedioxy group attached to adjacent carbon atoms; R 2 , R 2 <SP>1</SP> and R 2 <SP>11</SP> are each hydrogen, or two of them are hydrogen and the third is halogen, C 1-7 -alkyl, hydroxy, C 1-4 -alkanoyloxy, C 1-7  -alkoxy, C 1-7 - alkylmercapto, trifluoromethyl, nitro, amino, C 1-4 -alkanoylamino, C 1-7 -alkoxycarbonylamino or phenyl, or R 2  and R 2 <SP>1</SP> or R 2  and R 2 <SP>11</SP> together are methylenedioxy; R 3  is hydrogen or C 1-7 - alkyl; R 4  is hydrogen, C 1-7 -alkyl, C 1-7 -alkoxy- C 1-7 -alkyl, hydroxy-C 1-7 -alkyl, C 1-7 -alkylthio- C 1-7 -alkyl, C 1-7 -alkylsulfinyl-C 1-7 -alkyl, phenylthio - C 1-7  - alkyl, phenylsulfinyl - C 1-7  - alkyl, C 3-7 -alkenyl or halo-C 1-7 -alkyl, or R 3  and R 4  together are divalent C 1-4 -alkylene, -(CH 2 ) n -, where n is 3 or 4; and Z is -CHR 8 COR 5 , -CR 8 =CR 5 R 6  or -CHR 8 -CR 5 R 6 -OR 7 , where R 5  and R 6  are each hydrogen, C 1-7 -alkyl, phenyl or phenyl-C 1-7 -alkyl; R 7  is hydrogen, C 3-7 -alkanoyl, benzoyl, or benzoyl substituted by from one to three radicals selected from C 1-7 - alkyl, C 1-7 -alkoxy, hydroxy, halo and trifluoromethyl; and R 8  is hydrogen or C 1-7 -alkyl, and acid-addition salts thereof are prepared by heating, with formic acid in an inert organic solvent or with a benzyl di-C 1-7 -alkylammonium or a tri-C 1-7 -alkylammonium formate, a compound having the Formula II wherein Y is COR 5  or the group -CR 5 R 6 OH and R 5  can be hydrogen only in the latter group and R 8  in Formula II can be C 1-7 -alkyl only in the #-configuration, wherein Z in the compound obtained is -CHR 8 COR 5  or -CR 8 =CR 5 R 6 ; if desired, hydroxylating a compound of the Formula I obtained wherein Z is -CR 8  = CR 5 R 6  to prepare a corresponding compound of Formula I wherein Z is -CHR 8 -CR 5 R 6 OH; if desired, selectively reducing a compound of the Formula I obtained wherein Z is to prepare the corresponding compound wherein Z is -CHR 8 -CR 5 R 6 -OR 7  and R 6  and R 7  are hydrogen; if desired, reacting a compound of the Formula I obtained wherein Z is with an organo lithium compound R 6 Li, wherein R 5  and R 6  are each C 1-7 -alkyl, phenyl or phenyl- C 1-7 -alkyl, to prepare a corresponding compound of Formula I wherein Z is wherein R 7  is hydrogen; if desired, esterifying a compound of the Formula I obtained wherein Z is -CHR 8 -CR 5 R 6 -OR 7 , where R 7  is hydrogen to obtain the corresponding compound wherein R 7  is C 1-4 -alkanoyl, benzoyl or substituted benzoyl; if desired, debenzylating a compound of the Formula I obtained wherein R 1  is benzyl to obtain the corresponding compound wherein R 1  is hydrogen; if desired, alkylating a compound of the Formula I obtained wherein R 1  is hydrogen to obtain the corresponding compound wherein R 1  is other than hydrogen; if desired, esterifying a compound of the Formula I obtained wherein R 2 , R 2 <SP>1</SP> or R 2 <SP>11</SP> is hydroxy to prepare the corresponding compound wherein said radical is C 1-4 -alkanoyloxy; if desired, hydrolysing a compound obtained wherein R 2 , R 2 <SP>1</SP> or R 2 <SP>11</SP> is C 1-4 - alkanoylamino or C 1-7 -alkoxycarbonylamino by heating with aqueous alkali to prepare the corresponding compound wherein said radical is amino; if desired, nitrating a compound obtained in which R 2 , R 2 <SP>1</SP> or R 2 <SP>11</SP> is hydrogen, Z is -CHR 8 -COR 5  and R 1  is hydrogen to a corresponding compound in which R 2 , R 2 <SP>1</SP> or R 2 <SP>11</SP> is nitro; if desired, reducing a compound of Formula I obtained where R 2 , R 2 <SP>1</SP> or R 2 <SP>11</SP> is nitro to the corresponding compound wherein said radical is amino; and if desired, converting a basic compound obtained to an acid-addition salt thereof. Pharmaceutical compositions having central nervous system depressant activity comprise, as active ingredient, a 1,2,3,4,5,6-hexahydro-2,6- methano-3-benzazocine of the general Formula I or an acid addition salt thereof, together with a suitable carrier.