1.2.3- Triazolo azepines

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Treatment of a mixture of 6-methoxy-9-chloro-7//- and 6-methoxy-9-chloro-5//-pyrido[2,3-c]-azepine (20) (see Section 3.2.1.5.5.1) with 1-acylhydrazines yields 3-substituted 5//-pyrido[2,3-c][l,2,4]triazolo[4,3-a]azepines, e.g. 21.191 Likewise, with sodium azide in dimethyl sulfoxide, the tetrazolo[4,5- ]azepine 22 is formed in good yield. 

Garanti et al. (30a) reported a synthesis of the l,2,3-triazolo[l,5-a][4.1]benzox-azepine 149 via an intramolecular cycloaddition of an aryl azide with an acetylene (Scheme 9.30). By using a similar strategy, the l,2,3-triazolo[l,5-a][l,4-l ]benzo-diazepine 150, an analogue of Flumazenil, was also reported (30b,c). As an extension of this method, the l,2,3-triazolo[l,5-a][l,4]benzodiazepine-6-one 153 was synthesized using an intramolecular 1,3-dipolar cycloaddition of an azide with a cyano group (30d). 

Several unique heterocyclic fused-1,2,4-triazole structures have been published. Pyridine amination of 216 with O-mesitylenesulfonylhydroxylamine followed by condensation with various aryl and heterocyclic aldehydes and subsequent cyclization and oxidation gave triazolopyridines 217 <03TL1675>. Triazolopyridines 217 were utilized in the direct conversion to the triazolopyridine amides 218 with methylaluminoxane premixed with amines in a combinatorial library synthesis. A convenient synthesis of novel 4-(l,2,4-triazol-l-yl)-2-pyrazolines and their derivatives has been reported <03SC1449>. A novel triheterocyclic ring system, thieno[2,3-y][l,2,4]triazolo[l,5-a]azepines, has been published <03S1231>. 

These compounds were obtained (70S433) by cyclization of 2-hydrazinoazepines such as 2-hydrazino-3,4,5,6,7-pentahydroazepine (525) with A -dichloromethylene benzamide to give 3-benzoylamino-l,2,4-triazolo[4,3-a]5,6,7,8,9-pentahydroazepine (526). Reaction of methyl chloroformate, phosgene, or thiophosgene with the 3,4,5,6,7-penta-hydroazepin-2-one arylhydrazones (527) afforded (80USP4213773) the 3-0X0- or 3-thioxo-5,6,7,8,9-pentahydro-l,2,4-triazolo[4,3-a]azepines (528). 

Triazolo [2, 3 I,2]pyrimido[4,5-fe]azepine (523) was obtained in 83% yield from 2-hydrazinopyrimido[4,5-b]azepine 521 by heating with triethyl orthoformate for 3 hr (85CB863). It was suggested that the isomeric triazolo [4, 3 l,2]pyrimido[4,5-h]azepine (522) was first formed, which then underwent a Dimroth rearrangement to give 523. 

W. Daum, 1984, Derivatisierung von 2,5,6,7,8,9-Hexahydro-3H-triazolo[4,3a]azepin-3-on, Internal Report, Bayer AG, Uerdingen, Germany. 

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