Azabenzocycloheptenones. Part 20. Synthesis and utilisation of 4-amino-1,2,3,4-tetrahydro-1(1H)-benzazepines

Abstract

1,2,3,4-Tetrahydro-6- and -7-methoxy-4-oxo-1-(p-tolylsulfonyl)quinolines 3 (R = tosyl, X = 6- and 7-OMe) and 1-ethoxycarbonylmethyl-1,2,3,4-tetrahydro-7-methoxy-4-oxoquinoline 3 (R = CH₂CO₂Et, X = 7-OMe) have been ring-expanded in two steps to 2,3,4,5-tetrahydro-7- and -8-methoxy-4-oxo-1-(p-tolylsulfonyl)-1H-1-benzazepines 2 (R = tosyl, X = 7- and -8-OMe) and 1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-8-methoxy-4-oxo-1H-1-benzazepine 2 (R = CH₂CO₂Et, X = 8-OMe). Reduction of the oximes gives 4-amino-2,3,4,5-tetrahydro-7-methoxy-1-(p-tolylsulfonyl)-1H-1-benzazepine 1 (R = tosyl, X = 7-OMe), 4-amino-2,3,4,5-tetrahydro-8-methoxy-1H-1-benzazepine 1 (R = H, X = 8-OMe) and 4-amino-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-8-methoxy-1H-1-benzazepine 1 (R = CH₂CO₂Et, X = 8-OMe). From these, several N-substituted and N,N-disubstituted compounds have been obtained and 3-amino-2,3,4,5-tetrahydro-1-(p-tolylsulfonyl)-1H-1-benzazepine 12 (X = NH₂, Y = H) has been made by similar means. Two routes are described to 2,3,4,5-tetrahydro-8-methoxy-5-oxo-1-(p-tolylsulfonyl)-1H-1-benzazepine 13 (R¹ = tosyl, R² = H) which is converted to 2,3,4,5-tetrahydro-8-methoxy-4-methoxyimino-5-oxo-1-(p-tolylsulfonyl)-1H-1-benzazepine 17 (R = Me) and thence to 5-[2-(ethoxycarbonyl)ethynyl]-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-methoxyimino-1-(p-tolylsulfonyl)-1H-1-benzazepine 18 (R = CCCO₂Et) and 5-[2-(ethoxycarbonyl)ethyl]-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-methoxyimino-1-(p-tolylsulfonyl)-1H-benzazepine 18 [R = (CH₂)₂CO₂Et]. Reduction of oximino ketone 17 (R = H) in two steps gives both cis- and trans-4-acetamido-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-1-(p-tolylsulfonyl)-1H-1-benzazepines 22 and 21 which are separately deacetylated and cyclised with ethyl chloroacetate to cis- and trans-2,3,4,4a,5,6,7,11b-octahydro-9-methoxy-3-oxo-7-(p-tolylsulfonyl)[1,4]oxazino[3,2-d][1]benzazepine 26 and 25. By similar methodology cis- and trans-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-propionamido-1-(p-tolylsulfonyl)-1H-1-benzazepines 28 and 27 have been obtained, separated and the latter reduced to trans-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-(n-propylamino)-1-(p-tolylsulfonyl)-1H-1-benzazepine 29. In three steps the latter is converted to trans-2,3,4,4a,5,6,7,11b-octahydro-9-methoxy-4-(n-propyl)-7-(p-tolylsulfonyl)[1,4]oxazino[3,2-d][1]benzazepine 33.