Pyrrolo diazepines, synthesis

Pyrrolo[3,4-c][l,3]diazepine, dihydrosynthesis, 4, 287 Pyrrolo[l,3]diazepines synthesis, 7, 607 Pyrrolodiazines, 3-formyl-synthesis, 4, 511 Pyrrolo[3,2-c][l,2]dithioles occurrence, 6, 810... 

Transformation of 5-aminopyrazoles into 5-(pyrrol-l-yl)pyrazoles has been achieved by means of 2,5-dimethoxytetrahydrofuran <94EJM233> which is the first step for the synthesis of pyrazolo-[4.3-/]pyrrolo[l,2-fl]diazepines, a new class of anxiolytics (see Section 3.01.13.2). Pyrazole 5-iminophosphoranes have been used by Wamhoff <94JOC3985> as starting materials for the synthesis of zwitterionic heteropolycyclic pyrazoles. 

Without doubt, the most useful pyrazole synthons for building fused heterocyclic systems are aminopyrazoles. For instance, l-methyl-4-cyano-5-aminopyrazole is the starting material for the synthesis of pyrazolo [4,3-/]pyrrolo[l,2-a][l,4]diazepines which possess anxiolytic activity <94EJM233) l-phenyl-3-methyl-4-nitroso-5-aminopyrazole has been used to prepare imidazo[4,5-... 

There is an increasing interest in the synthesis of fused diazepines with potential anti-tumour activity. A new direct synthesis of pyrrolo[2,l-c][l,4]-benzodiazepin-5-ones, e.g. (105), has been developed en route to a complete synthesis of the anti-tumour antibiotic sibiromycin. Two routes have been devised to the novel pyrrolo[l,2- f][l,4]benzodiazepin-6-one system, but members of this series were inactive as sedative, depressive, or myorelaxant agents. ... 

Further variations have been reported on the synthesis of pyrrolo-[l,2-a]thieno[3,2-/]-l,4-diazepin-4-ones, giving the 6-alkoxy-" and the... 

The susceptibility of the pyrrole ring to electrophilic attack has been used in the synthesis of pyrrolo-fused 1,4-diazepines, for example, A-(3-acetylaminopropyI)-3-methyl indole underwent a Bischler-Napierelski-type cyclodehydration on treatment with phosphorous oxychloride in benzene to give ll-methyl-4,5-dihydro-3ff-l,4-diazepine[l,2-a]indole <91IJC(B)1018>. In another example the acyl azide (143) cyclized to the furo[2,3-e]pyrrolo[l,2-a]-l,4-diazepine-9-one (144) (Scheme 25) <92JHC1507>. 

This methodology with some variations has been utilized in the synthesis of numerous heterocyclic systems, such as heterocycle-fused quinolinone derivatives [391], l,4-benzodiazepin-2-ones [392], benzo-, naphtho- and heterocycle-fused pyrrolo[2,l-c][l,4]diazepines [393], quinolinone or pyrrolidinone derivatives [394], dibenzo[fl,c]phenanthridines [395], thiazolo-fused quinolinones [396], isoindolinone and isoquinolin-2-one derivatives [397], indoline derivatives [398], 5-aroyl-pyrrolidinones [399,400], indazolone derivatives [401,402], substituted indolizidinones [403], 1-arylpyrrolopyrazinones [404], stmcturally diverse... 

Diazepines have attracted considerable attention in 1980, as befits their commercial importance as antidepressents and in other medicinal applications. Work appeared from Roche describing further investigations into the industrial preparation of the antidepressants, and another group prepared a pyrrolo-benzo[l,4]diazepinone in an analogous manner.Possibly of more interest were two reports on the preparation of 1,3-diazepines which are not so common. Ishikawa et reported the synthesis of (424) by standard methods, and Coyle etal produced (426) by acid-catalysed cyclodehydration of the hydroxy-benzamide (425) in >80% yield. Phthalimide Mannich bases have been widely investigated by several groups in analogous conversions as discussed earlier. 

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