Benzoazepines

Scheme 9.11. Synthesis of 2,5-diketopiperazines 9-57 and 1,4-benzoazepine-2,5-diones 9-58 by an Ugi-4CR process.

Tandem mass spectrometry has been used to demonstrate that M+ as well as MH+ of substituted A-(ort/zo-cyclopropylphenyl)benzamides isomerizes before the fragmentation, with formation of 3-aryl-1-ethyl-lH-benzoxazines and 5-ethyl-2-oxodi-benzoazepines (Scheme 5.14). The methyl group in /V-[ortho-( 1 -methylcvclopropyl )-phenyl]benzamides quenches the latter process, leaving the formation of benzoxazines as the only cyclization reaction. A subsequent chemical experiment in solution confirmed the mass spectral predictions [24]. A similar study confirmed the analogy of cyclization of substituted A-(ort/zo-cyclopropylphenyl)-A -aryl ureas and N- ortho-cyclopropylphenyl)-A -aiyl thioureas in the ion source of mass a spectrometer and in solution [25]. 

In this case, aprotic bipolar solvents and triethylamine are employed. Thus, interaction of perfluoro-2-methylpent-2-ene with 2-aminophenol in the presence of triethylamine in diethyl ether affords 4-fluoro-2-(pentafluoroethyl)-3-(trifhaoromethyl)-l,5-benzoazepine 154 (80JFC(16)75). 

Pentacyclic derivatives 48 of the benzoazepine (-)-clavizepine were synthesised using three different methods for the formation of the azepine ring including radical, palladium and Friedel-Crafts alkylation and acylation, the most successful being the latter. <07JOC8804>. 

A benzazepine derivative of homopipecolic acid 53 was formed by the reaction of an A-magnesioaryl amine with a magnesium carbenoid formed from 1-chloroalkyl p-tolyl sulfoxide 51. The intermediate 52 was trapped with ethyl chloroformate to yield the benzoazepine in good yield. In contrast, the corresponding azepine derivative was formed in only 4% yield <07TL7829>. 

Chloro-1-(4-fluoro-phenyl)-7-methyl- 1437 C,4H, CINOj lH-2-Benzoazepine... 

Matsuhisa. A., Kikuchi, K.. Sakamoto, K.. Yatsu. T.. and Tanaka, A., Nonpeptide arginine vasopressin antagonists for both V[ and V, receptors. Synthesis and pharmacological properties of 4 -[5-(substi-tuted methylidene)-2,3.4.5-lclrahydro-l/y-l-benzoazepine-l-carbonyl]benzanilide and 4 -[5-(substi-tuted methyl)-2,3-dihydro-l//-l-benzoazepine-l-carbonyl]benzanilide derivatives, Chem. Pharm. Bull.. 47. 329, 1999. 

Keywords NMDA Glycine antagonists Stroke Indole-2-carboxylates Benzoazepines Pyrido[2,3-()]pyrazines... 

Fig. 4. General structures of pyrido[2.3-fc]pyrazines (7), indole-2-carboxylates (8) and benzoazepines (9).

Fabio et al., 1997 and references cited therein). Among others, a novel series of benzoazepine derivatives of general structure (16), bearing the same a,(3-unsaturated side chain as GV150526 at the position C-5 (Fig. 6) and different substituent at C-3 was proposed. A number of different compounds was then prepared and evaluated and results are reported in Table 3 (Di Fabio et al., 1999a). 

Affinity of benzoazepine derivatives for the strychnine-insensitive binding site... 

A novel ring expansion of quinolines for the synthesis of benzoazepines was reported by Yadav and coworkers. Quinolines 76 (Scheme 34) were reacted with various diazocarbonyl compounds 77 in the presence of copper(II) triflate to generate the seven-membered azepine ring system 78 in good yields. Isoquinolines were also shown to undergo ring expansion under the same conditions <04CC2124>. 

Benzoazepines and benzodiazepines are another recurring privileged scaffold in agonists and antagonists of... 

Benzo- as well as heteroaromatic systems were obtained allowing for a variable substitution pattern in the benzoazepine frameworks. To access the dibenzo-diazepine or dibenzoxazepinone frameworks according to C-N cross-coupling methodology, a different strategy had to be pursued. The introduction of the nitrogen atom or the amide functionaHty was accompHshed by the condensation of ammonia with keto- or ester-carbonyl frmctionaHties (Scheme 13.96 and Scheme 13.97) [142],... 

The reaction takes place via C-C insertion and leads to novel benzoazepines such as ethyl l//-benzo[fi]azepine-l-carboxylate and ethyl 3//-benzo[d]azepine-3-carboxylate, in excellent yields with a high degree of selectivity. Similar results were observed using 10 mol% of Rh2(OAc)4. It is noteworthy that no reaction was observed with other metal trifiates such as Sc(OTf)3, Yb(OTf)3, and In(OTf)3. 

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