Azabenzocycloheptenones. Part 20. Synthesis and utilisation of 4-amino-1,2,3,4-tetrahydro-1(1H)-benzazepines
Azabenzocycloheptenones. Part 20. Synthesis and utilisation of 4-amino-1,2,3,4-tetrahydro-1(1H)-benzazepines
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氮杂苯并环庚烯酮。
DOI：
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
D. Scopes
中科院分区：
文献类型：
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作者：
K. Booker‐Milburn;I. Dunkin;F. C. Kelly;A. Khalaf;D. Learmonth;G. Proctor;D. Scopes
1,2,3,4-四氢-6-和-7-甲氧基-4-氧代-1-(对甲苯磺酰基)喹啉 3 (R = 甲苯磺酰基, X = 6- 和 7-OMe) 和 1-乙氧基羰基甲基-1,2,3,4-四氢-7-甲氧基-4-氧代喹啉 3 (R = CH2CO2Et, X = 7-OMe) 已分两步扩环为 2,3,4,5-四氢-7- 和 -8-甲氧基-4-氧代-1-(对甲苯磺酰基)-1H-1-苯并氮杂 2 (R = 甲苯磺酰基, X = 7- 和 -8-OMe) 和1-乙氧基羰基甲基-2,3,4,5-四氢-8-甲氧基-4-氧代-1H-1-苯并氮杂2（R = CH2CO2Et，X = 8-OMe）。肟还原得到 4-氨基-2,3,4,5-四氢-7-甲氧基-1-(对甲苯磺酰基)-1H-1-苯并氮杂 1 (R = 甲苯磺酰基, X = 7-OMe), 4-氨基-2,3,4,5-四氢-8-甲氧基-1H-1-苯并氮杂 1 (R = H, X = 8-OMe) 和 4-氨基-1-乙氧基羰基甲基-2,3,4,5-四氢-8-甲氧基-1H-1-苯并氮杂 1 (R = CH2CO2Et, X = 8-OMe)。由此，获得了几种N-取代和N,N-二取代的化合物，并通过类似的方法制备了3-氨基-2,3,4,5-四氢-1-(对甲苯磺酰基)-1H-1-苯并氮杂12 (X = NH2, Y = H)。描述了 2,3,4,5-四氢-8-甲氧基-5-氧代-1-(对甲苯磺酰基)-1H-1-苯并氮杂 13 (R1 = 甲苯磺酰基，R2 = H) 的两条路线，将其转化为2,3,4,5-四氢-8-甲氧基-4-甲氧基亚氨基-5-氧代-1-(对甲苯磺酰基)-1H-1-苯并氮杂17 (R = Me) 5-[2-(乙氧基羰基)乙炔基]-2,3,4,5-四氢-5-羟基-8-甲氧基-4-甲氧基亚氨基-1-(对甲苯磺酰基)-1H-1-苯并氮杂18 (R = CCCO2Et) 和5-[2-(乙氧基羰基)乙基]-2,3,4,5-四氢-5-羟基-8-甲氧基-4-甲氧基亚氨基-1-(对甲苯磺酰基)-1H-苯并氮杂18 [R = (CH2)2CO2Et]。分两步还原肟基酮 17 (R = H) 得到顺式和反式-4-乙酰氨基-2,3,4,5-四氢-5-羟基-8-甲氧基-1-(对甲苯磺酰基)-1H-1-苯并氮杂22 和 21，分别将其脱乙酰基并用氯乙酸乙酯环化为顺式和反式-2,3,4,4a,5,6,7,11b-八氢-9-甲氧基-3-氧代-7-(对甲苯磺酰基)[1,4]恶嗪基[3,2-d][1]苯并氮杂26和25。通过类似的方法顺式和得到反式-2,3,4,5-四氢-5-羟基-8-甲氧基-4-丙酰胺基-1-(对甲苯磺酰基)-1H-1-苯并氮杂28和27，分离并将后者还原为反式-2,3,4,5-四氢-5-羟基-8-甲氧基-4-(正丙氨基)-1-(对甲苯磺酰基)-1H-1-苯并氮杂 29. 后者分三步转化为反式-2,3,4,4a,5,6,7,11b-八氢-9-甲氧基-4-(正丙基)-7-(对甲苯磺酰基)[1,4]恶嗪基[3,2-d][1]苯并氮杂 33.
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.