Pyrrolo 2,3-rf pyrimidines

Alkylation at position 5 of a pyrrolo[2,3-rf pyrimidine occurs via a Mannich reaction. The nucleoside 10 is transformed into the morpholinomethyl derivative 11 in modest yield (Equation 4) <199781067>. 

Chlorouracil, in its protected form, can be formally viewed as a precursor in pyrrolo[2,3-rf pyrimidine preparations. Thus 135 is treated with 136, which presumably gives a 6-amino intermediate by displacing the chloro group, and subsequently cyclizes to 137 (Scheme 13) <1995JOC5069>. 

Another furan precursor 161 has been used to generate a series of pyrrolo[2,3-rf]pyrimidine triones 162 (Equation 60) the furandiones react with aryl isocyanates, releasing 2 mol of carbon dioxide, to form compounds 162a-f <2004ASJ877>. 

A. PYRROLO[2,3-rf]PYRIMIDINE C-NuCLEOSIDES 1. Pyrrolo[2,3-d]pyrimidin-6-yl C-Nucleosides... 

Amidines have been shown to react with 2-amino-3-cyanofurans (16) to yield, not the expected furo[2,3-ethyl]benzoate (18) and guanidine give 2,4-diamino-5-[2-(4-carbethoxy-phenyl)ethyl]-pyrrolo[2,3- / pyrimidine (19) [95JOC6684J. 

However, treatment with dimethyl acetylenedicarboxylate gives only, in one example, the expected pyrido[2,3-rf]pyrimidine in all other cases the previously mentioned Michael-addition-ring cleavage-cyclization-condensation sequence is observed to afford pyrrolo[3,4-cJpyridine-diones (cf. Scheme 128) (88TL4401 89CB1673) (Scheme 163). 

The pyrrolo[2,3-d]pyrimidine (128) was obtained in 67% yield by the reaction of the pyrimidinone (127) with phosphorus oxychloride in DMF (77CHE1338), as shown in Scheme 27. An analogous reaction of the quina-zolinone (129) with an excess of thionyl chloride in DMF gives the pyrrolo[2,3-rf]quinazolinone (130) in good yield (73IJC532). 

Thiazolo[3,2-a]pyrrolo[2,3-Hantzsch thiazole synthesis has made compounds of the above... 

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). 

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