Indolo pyrimidines

Most unusual is the synthesis of y/c-triazolo[4,5-i/]pyrimidine (262) by heating 6-azido-l,3-dimethyluracil with potassium carbonate in DMF. Whereas intramolecular cyclization of an azide function onto C=N to give tetrazoles is well known, the corresponding formation of triazoles by addition to C=C is extremely rare. Also noteworthy are the 5-diazo-6-amino-uracils (263 R = Me, Et, or Ph), which, although table in boiling acetic acid, cyclize (with loss of nitrogen) in hot DMF to indolo[2,3-d]pyrimidines (264). Far superior are the photodecompositions of (263) which furnish the indolo-pyrimidines in quantitative yield. 

The photoelimination of nitrogen from diazo compounds provides a simple and versatile route for the generation of carbenes, and in certain instances, insertion reactions of carbenes can be employed in the synthesis of heterocycles. Carbenes are believed to be involved at least in part in the photochemically induced conversion of N,N-diethyldiazoacetamide (439) into the y-lactam 440 and the /Mactam 441,365 and a similar approach has been successfully employed in the synthesis of a carbapen-2-em366 and of 7-methylcephalosporin analogues.367 Carbene insertion of a different type has been observed on irradiation of the 6-anilino-5-diazouracils 442 to give the indolo[2,3-d]pyrimidines 443.368 Ring contractions in heterocycles... 

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

In a similar tandem reaction, ethyl 2-azido-l-methyl-l/7-indole3-carboxylate 364 is converted to indolo[3,2- ]l,2,3-triazolo[l,5- ]pyrimidin-5-ones 366 via triazole intermediates 365 that are not separated (Scheme 58). Products 366 are obtained in 80-90% yield as potential intercalates of DNA <2003H(60)2669>. 

Interaction of substituted dienediamines with ethylenediamine yields im-idazo[3,2-n]pyridine derivatives (95JHC477). 3-Arylaminoindoles, with distinct enamine properties, are the starting materials for the synthesis of indolo[3,2-b]quinoline derivatives [96KFZ(7)42]. a-Carboline derivatives can be obtained from enamine-based 3-dimethylamino-2-indolinones [96KFZ(9)35, 96KFZ(10)32], The synthesis and transformation of enamines based on the pyrido[l,2-n]pyrazine ring system into imidazo[l,2-n]pyridine and imidazo[l,2-a]pyrimidine derivatives have been reported... 

New approaches to the indole nucleus are continuously developed, providing aceess to indoles which are difficult to prepare using the well established reactions, such as the Fischer indole synthesis. Nevertheless, this classic reaction is still often used for constructing more complex systems, as exemplified by the preparation of 2-(pyrimidin-4-yl)indoles <03CPB975>, or indolo[3,2-i)]carbazoles possessing new substitution patterns <03T1265>. 

Nitrogen Heterocycles.- Reactions of iminophosphoranes have been used to prepare a wide range of heterocycles. Examples of compounds prepared by intramolecular aza-Wittig reactions include 3,4-dihydroquinazolines (191) and quinazolines (192), quinazoline derivatives (e.g. 193),pyrrolo( 1,2-a)quinoxalines (194), indolo[3,2-clquinolines (195), and indolo[l,2-c]quinazolines (196),"8 imidazolinones (197),"9 quinazolinones (198),"9, 120 pyrido[2,3-d]pyrimidine derivatives (199), 21 and 4,5-dihydropyrazolo(3,4-d]pyrimidine derivatives (200). 22 Tributyl(cyclohepta-1,3,5-trienylimino)phosphorane (201), prepared by thermal isomerization of the 2,4,6-derivative, reacts with a,p-unsaturated ketones to give 9H-cyclohepta[b]pyridine derivatives (202). 23 a synthesis of (2,4)pyridinophanes (204) by the reaction of N-vinyliminophosphoranes (203) with a,P-unsaturated ketones has been reported. 24... 

Aryl azides undergo indolization upon photolysis, and several examples are known (Scheme 8) [67-70]. Thus, p-phenyl-substituted (Me, OMe, Cl) azidopyrimi-dines 11 were converted to the corresponding 9H-pyrimido[4,5- ]indole (equation 1) [67, 68]. The azide precursor is in equilibrium with the ring-opened 8-phenyltetrazolo[l,5-c]pyrimidine (10) (in trifluoroacetic acid). Similarly, Da Settimo and colleagues synthesized the new ring system 67/-indolo[2,3- ][l,8]naphthyridine 12 by photolysis in trifluoroacetic acid of the equilibrium mixture of 4-phenyltetrazolo[l,5-fl][l,8]naphthyridines... 

Lauria A, Diana P, Barraja P, Montalbano A, Dattolo G, Cirrincione G (2004) Docking of indolo- and pyrrolo-pyrimidines to DNA. New DNA-interactive polycycles from amino-indoles/pyrroles and BMMA. ARKIVOC 5(2) 263-271... 

Palladium-catalyzed reaction of bis(o-trifluoroacetamidophenyl) acetylene 685 with various aryl and vinyl halides and triflates led to the formation of indolo[l,2-c] quinazolines 686 (Scheme 143) [406]. If the reaction was performed in presence of CO, the corresponding acyl derivatives 687 were obtained [407], In both cases, the indole heterocyclic system was formed first the subsequent pyrimidine ring closure resulted in construction of the tetracyclic ring system. 

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