4- Amino-7- -5//-pyrrolo pyrimidine

The pyrrolo[2,3-d]pyrimidine 67 ring system can be obtained from 4-amino-substituted pyrimidine oxime 66 and Dowex-50 in water (equation 28) . Similar cyclization was realized in the presence of benzaldehyde and concentrated HCl . ... 

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). 

Ibbercidin Streptomyces tubercidicus 4-Amino-7-pyrrolo- pyrimidine Ribose Adenosine... 

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... 

In addition, Namazi and coworkers expanded the DHPM core by constructing pyrrolo[3,4-rf pyrimidines via the classical approach. First, DHPM 59 was delivered in 60% yield using the standard Biginelli conditions. 59 was then brominated in high yield to afford 60. Substitution of bromide 60 with methylamine followed by cyclization of the intermediate amino ester furnished pyrrolo[3,4-rf pyrimidine 61 in 53% yield. 

Besides furo[2,3-d]pyrimidines, 6-substituted 5H-pyrrolo[2,3-h]pyrazines have also been obtained in a microwave-promoted one-pot process starting from N-mesyl protected 2-amino-3-chloropyrazine (Scheme 60) [74]. The... 

Other pyrimidines with variations at positions 2 and 4 have also been used to generate specific pyrrolo[2,3-t7 -pyrimidines. The condensation of 6-amino-4-hydroxy-2-methylthiopyrimidine 109a with 2-chloro-4-acetoxybutanal in aqueous NaOAc gives the fused ring product 110 (Scheme 11) <1998J(P1)3565>. 

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>. 

When an amino group is adjacent to a carboxamide group, annulation usually leads to a pyrrolo[2,3-r/ pyrimidin-4-one 164. Such is the case when 163 is allowed to react with aliphatic carboxylic esters (Equation 61) <1996H(42)691>. 

The most common approach to the synthesis of a fused pyrimidine ring involves condensation reactions between adjacent carboalkoxy and amino groups. Therefore, it is not surprising that the majority of pyrrolo[3,2-4]pyrimidines that involve a pyrrole precursor follow this pathway. 

A useful pyrimidine precursor is 2,4-diamino-6-oxo-pyrimidine. Heating a mixture of this pyrimidine and l-bromo-2-butanone in DMF afforded 2-amino-6-ethyl-3,4-dihydro-4-oxo-7(7/)-pyrrolo[2,3-,y pyrimidine in modest yield <2006JMC1055>. 

Likewise 3-amino-2-cyano-4-(3-methoxyphenyl)-A -carboethoxypyrrole is converted into 7-(3-methoxyphenyl)-pyrrolo[3,2- pyrimidin-4-one by, first decarboxylation, and then cyclization in refluxing formic acid <2006BMCL2091>. Replacing the 3-methoxyphenyl group on the pyrrole with a reduced pyrrole (a mimic of a ribofuranose ring) leads to a 4-aminopyrrolo[3,2- pyrimidine when treated with formamidine acetate <2006BMCL2662>. 

Finally, ortho aminoesters have been used to produce 7-deazaxanthines. For example ethyl 2-amino-5-phenyl-l//-pyrrole-3-carboxylate is first treated with 2-chloroethyl isocyanate in refluxing toluene. The resulting urea derivative is then allowed to react with l-(2-methoxyphenyl)piperazine and cyclized to the expected pyrrolo[2,3-,7 pyrimidin-2,4(177,377)-dione <2006BMCL150>. 

Few completely assigned 13C spectra are available at the time of writing, but it is instructive to compare the chemical shifts for pyrrolo[2,3-(/]pyrimidine (8) (75JA4627) with those of its 6-amino-2-methyl-4-oxo derivative (12 Scheme 2) (78JOC3937). 

The H NMR spectra for several 6-amino-2-phenylpyrimido[5,4-c]pyridazin-8-ones have been reported. A common feature in these compounds is the appearance of a pair of doublets at 5 9.2 (H-3) and 7.4 (H-4) (/3>4 = 7.1-7.6 Hz). These data are contrasted with data obtained for several corresponding pyrrolo[3,2-cf]pyrimidines (78JOC2536). 

The reactions with the aminocyanofiirans produced an unexpected result, however, as illustrated by the following example. 2-Amino-3-cyano-4-methylfuran was added to a solution of guanidine free base in ethanol, and the mixture was heated under reflux for 24 hours. Standard work-up gave the pyrrolo[2,3-d]pyrimidine 3 in 67% yield, and not the expected furo[2,3-[Pg.146]

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. 

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