Synthesis and utilisation of 6-aminotetrahydrobenzo[7]annulenes

Abstract

7,8-Dichloro-1,2,3,4,5,6-hexahydrobenzo[ f ]quinolin-3-one 10 (R = H) is obtained by reaction of 5,6-dichloro-3,4-dihydronaphthalen-2(1H)-one pyrrolidine enamine 9 with acrylamide and is N-alkylated to 7,8-dichloro-1,2,3,4,5,6-hexahydro-4-propylbenzo[ f ]quinolin-3-one 10 (R = Prⁿ). 6,7,8,9-Tetrahydro-2-methoxy-5H-benzo[7]annulen-6-one 5 (R = H) is converted to N,N-dipropyl(6,7,8,9-tetrahydro-2-methoxy-5H -benzo[7]annulen-6-yl)amine 8 and via the pyrrolidine enamine is reacted with acrylamide to give 2,3,4,5,6,7-hexahydro-9-methoxy-1H-benzo[3,4]cyclohepta[1,2- b]pyridin-3-one 11 (R = H) and 2,3,4,4a,5,6-hexahydro-8-methoxy-1H-benzo[5,6]cyclohepta[1,2- b]pyridin-2-one 12 (R = H). Each of these is N-alkylated to give 11 (R = Prⁿ) and 12 (R = Prⁿ) which are reduced individually to 2,3,4,4a,5,6,7,11b-octahydro-9-methoxy-4-propyl-1H-benzo[3,4] cyclohepta[1,2-b]pyridine 14 (X = Y = H) and 2,3,4,4a,5,6,11,11a-octahydro-8-methoxy-1-propyl-1H-benzo[5,6] cyclohepta[1,2-b]pyridine 15 (X = Y = H) respectively. The hydroxyimino derivative 19 (R = H) of 6,7,8,9-tetrahydro-1,2-dimethoxy-5H-benzo[7]annulen-5-one 18 is methylated to give 19 (R = Me) which with ethyl lithiopropiolate yields ethyl 3-(6,7,8,9-tetrahydro-5-hydroxy-1,2-dimethoxy-6-methoxyimino-5H -benzo[7]annulen-5-yl)propiolate 20 which is catalytically reduced to 21. 6,7,8,9-Tetrahydro-1,2-dimethoxy-6-propionamido-5H-benzo[7] annulen-5-one 22 prepared from 19 (R = H) is reacted with sodium borohydride to give both cis- and trans-6,7,8,9-tetrahydro-5-hydroxy-1,2-dimethoxy-6- propionamido-5H-benzo[7]annulen-5-ol 24 and 23 which are separately reduced by BH₃–THF to cis- and trans-6,7,8,9-tetrahydro-5-hydroxy-1,2-dimethoxy-6- propylamino-5H-benzo[7]annulen-5-ol 26 and 25. The latter is reacted with chloroacetyl chloride and thence in two steps gives trans-2,3,4,4a,5,6,7,11b-octahydro-8,9-dimethoxy-4- propylbenzo[6,7]cyclohept[1,2-b][1,4]oxazine 29.