Pyrrolo pyrimidines, formation

Not surprisingly, one of the most common reactions of pyrrolo[2,3- ]pyrimidines is nucleoside formation. Typical of the process is the reaction of 5 with the fluorine-containing carbohydrate moiety 6 to produce the nucleoside 7 (Scheme 1) <1995JME3957>. Numerous other reports are described in the literature but the number is too large to be cited here. 

Another example of the simultaneous formation of both the pyrrolo and furo compounds has been observed. Nearly identical yields of 102c and 103b were isolated <2005JME5329>. Nonetheless, other 6-substituted derivatives of pyrrolo[2,3- pyrimidines have been prepared without complication, for example, 102d <2001JHC349> and a variety of arylmethyl compounds, illustrated by 102e <2003BMC5155>. 

Azine A-oxides and azine A-imides undergo a deep ring transformation on interaction with various dipolarophiles. Thus, fervenulin-4-oxides (423) react with DMAD to afford derivatives of pyrrolo[3,2-first step of the reaction is assumed to involve the formation of cycloaddition products (424) which transform by subsequent multi-stage process into (425) (79JOC3830). 

Alkoxy groups are convenient substituents in the primary synthesis of fused pyrimidines. These allow the formation of oxo derivatives to proceed smoothly. One example of this is the hydrolysis of the 4-methoxy derivative by hot aqueous hydrochloric acid to give the 3//,5//-pyrrolo[3,2-d]pyrimidin-4-one (22) which is a deazahypoxanthine <92JCS(P1)1883>. 

The classic approach to the formation of a fused pyrimidine ring involves cyclization of adjacent amino and cyano (or carbalkoxy) groups. The formation of pyrrolo[3,2-d] pyrimidines, commencing with a suitably substituted pyrrole, follows this route exclusively. Virtually all of the activity using this approach involves the formation of C-nucleosides. 

The use of pyrimidines as precursors for pyrrolo[3,4-rf]pyrimidines is the most common synthetic approach. 6-Phenyl-7-(substituted)amino-pyrrolo[3,4-ii]pyrimidine-2,4(l//,3//)-diones (164) are readily obtained from the reaction of 5-formylpyrimidines (163) with arylamines (Equation (54)) <89BCJ3043>. Formation of the Schiff base, followed by cyclization, is the proposed pathway. A more traditional approach is found in the conversion of the cyanoester (165), via the amide, to the corresponding pyrrolopyrimidine (166) (Equation (55)) (88LA643). 

Photochemically induced ring contraction of novel 4-iminodi-hydro-1,2,3-triazoles to the corresponding ( )- and (Z)-aziridin-imines has also been reported. A different pathway is followed in the 6-(l -triazolyl)uracils (24) which on irradiation in acetonitrile were converted into the pyrrolo[2,3-d]pyrimidines (25) via triplet biradical intermediates a novel cyclisation leading to the formation of pyrimido[4,5-c]isoquinolines is observed, however, when C-5 phenyl substituents are present on the triazole ring. Rate constants for the cycloaddition f diarylnitrilimines, generated by photoelimination of nitrogen from diaryl 2H-tetra-zoles, to various dipolarophiles have been determined experiment-... 

The formation of a nitrene adjacent to a double bond can be used in the synthesis of novel heterocyclic systems. For example, the azide 721 converts smoothly into the tricyclic product 722 on irradiation and the same modus operandi is used for the synthesis of pyrrolo[2,3-J]pyrimidines from substituted 4-azidopyrimidines . Aziridine formation is also encountered in the cyclization of 723 to the tetrahydroquinoline derivatives 724 . Other cyclizations provide routes to imidazoindoles 725 " or thienopyrroles 726 . ... 

Pyrrolo[3,4-ring-closure of 4-dialkylamino-3-benzoylpyrroles with urea, as illustrated by the formation of compound (329) from (328) (Scheme 127). Monomethylated derivatives of allopurinol, e.g. (331), are obtained via 4-(methylthio)pyrazolo[3,4-[Pg.267]

In another work, fluoromethyl group in pyrimidines 1225 acted as CH-acid in an intramolecular condensation with carbonyl compound, leading to the formation of 8-fluoro-pyrrolo[l,2-a]pyrimid-4-one derivatives 1226 (Schane 268) [358,756],... 

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