Substituted benzo pyrrolo

Debenzylation on the side-chain with TMSl to produce substituted benzo[/]pyrrolo[l,2-d][l,4]diazepinone 181 has been reported (Scheme 36, Section 3.1.1.1 a992BMCL1639)). 

Few examples of the intramolecular electrophilic substitution on a C2py oie site have been reported for benzo[/]pyrrolo[l,2-a]azepinones. Thus, treatment of acid 62 with phosphorous pentachloride results in Friedel-Crafts product 63 (Scheme 13 (2000T9351)). 

N-Alkyl isoindolo[2,l-fc][2,4]benzodiazepines 190 (R = alkyl. Scheme 38, Section 3.1.1.2) are synthesized by an intramolecular N-acyliminium ion-amide reaction (1997TL2985, 1998T1497). Isothiocyanates 23 undergo under basic conditions in DMF ring closure by an intramolecular substitution between N1 of the pyrrole ring and isothiocyanate group to afford benzo[/]pyrrolo[l,2-c] [l,3]diazepine-5-thiones 25 (Scheme 2, Section 2.1.1.1 (2005BMCL3220)). 

Alkylation of pyrrolo-benzodiazepine dione 244 with methyl iodide occurs on both positions N9 and ClOa, while reaction with 2-bromo diethylaminoethane leads to the low yield of the 4-substituted 248. Acylations with benzoyl and 2-chloroacetyl chlorides are directed exclusively to position 4 to afford 247 (Scheme 52, Section 3.1.1.4 (1992CE649, 2005H2451)). Alkylation of 5H-benzo[/]-pyrrolo[l,2-d][l,4]diazepin-6(7H)-one with a substituted phenethyl bromide has been reported (Scheme 36, Section 3.1.1.1 (1992BMCL1639)). 

Intramolecular electrophilic reactions of substituted pyrrole-2-carboxylic acids or their amides lead to benzo[d]pyrrolo[l,2-a]azepinones. Acid 70 in this fashion undergoes Fiiedel-Crafts cyclization to furnish fused azepine 71 in good yield (Equation (6) (2000JOC2479)). 

Several azepine ring constructions have been reported using palladium catalyzed C-C bond formation. Palladium catalyzed cyclizations of substituted tryptamine derivatives 73 lead to benzo[d]pyrrolo[l,2-a]azepinones 74 (Equation (8) (2000JMC1050)). 

Reaction of the radical derived from substituted 2-bromo indole 78 leads in moderate (37%) yield to benzo[d]pyrrolo[l,2- ]azepinone 79 along with 32% of the reduction product 80. The process occurs via radical addition to the benzene ring followed by rearomatization (Equation (9) (2000TL4209)). 

Amino methyl substituted pyrrolo-benzodiazepine 215 forms a cyclic aminal with aldehydes that can be further oxidized with Mn02 to fused 3-substituted imidazole 216. Alternatively, cyclic imine 217 can be submitted to TosMlC cycli-zation to afford unsubstituted 9H-benzo[e]imidazo[5,l-c]pyrrolo[l,2-fl][l,4]-diazepine 218 (Scheme 45, Section 3.1.1.2 (1993JHC749)). 

Benzo[e]thieno[3,2- ]thiepin-10(5Ef)-one 388 can be smoothly reduced with sodium borohydride to the corresponding alcohol, which forms the chloro substituted compound under standard treatment with thionyl chloride (1991CPB2564). Dihydro derivatives of pyrrolo-benzothiazepine 377 have been reported starting from ketone 373 by a carbonyl reduction, bromination and amination sequence (Scheme 76, Section 5.1.1 (1998JMC3763, 2002JMC344, 2004JMC143)). 

An intramolecular reaction with primary amine as the nucleophile that was prepared in situ by the reduction of the nitro group in pyrrole 1319 resulted in the pyrrolo[2,Tf]benzo[/ ]diazepine 1320, which indicates that the amino group reacts via condensation with the aldehyde group rather than via substitution of the chloro group (Equation 287) <2005T5831>. 

Unexpected results were obtained when chromenone-based cyclophanes was treated with DBU to achieve HNO elimination, followed by DDQ oxidation to give benzo[fo]furan-based cyclophanes as shown below <05TL8789>. DDQ oxidative conversion of (Q-p-[2-hydroxyphenylethylene]benzeneethanol into 2-phenylbenzofuran was also reported . In addition, an unusual rearrangement of substituted 2-phenylbenzo[d]pyrrolo[3,2-fo]pyrylium perchlorate to 2-phenylfuro[23-c]isoquinoline was observed <05SL1036>. 

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... 

As a result of electrophilic substitution reaction were isolated monosubstituted products (V-VIII) 3-phenylazo- (V), 3-(p-nitrophenylazo)- (VI), 3-(p-chlorophenylazo)-(VII), 3-(p-bromphenylazo)- (VIII), 3-(p-iodphenylazo)-(IX), 3-(p-sulphamidephenylazo)-lH,10H-benzo[e]pyrrolo[3,2-g]indole (X), 2-phenylazo- (XI), 2-(p-chlorophenylazo)- (XII) and 2-(p-nitrophenylazo)-3H,8H-indolo[4,5-e]indoles (XIII). 

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