Pyrrolo pyrimidines, synthesis

H-Pyrrolo[3,2-d]pyrimidines synthesis, 3, 345 Pyrrolo[3,4-d]pyrimidines synthesis, 4, 524 Pyrrolopyrimidinones synthesis, 4, 518... 

Pyrrolo[3,2-h]pyrimidines, synthesis, reactivity, and biological activity of 86KFZ7I3. 

Pyrrolo[2,3-d]pyrimidine, 5-cyano-bromination, 4, 506 Pyrrolo[2,3-d]pyrimidine, 5-nitroso-nucleophilic reactions, 4, 507 Pyrrolo[l, 2- c]pyrimidine-3-carboxylic acids methyl ester synthesis, 4, 293 Pyrrolopyrimidine-2,4-diones Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolopyrimidines synthesis, 4, 514, 517, 524, 527 Pyrrolopyrimidines, chloro-nucleophilic attack, S, 312 Pyrrolo[2,3-d]pyrimidines NMR, 4, 500... 

The synthesis of some novel acyclonucleosides involving pyrrolo[2,3-c]pyridazine and a 4-hydroxybutyl side chain has been reported <00H(53)5>. New pyrrolo[2,3-pyrimidines containing an extended 5-substituent, as potent and selective inhibitors of lck (an src-family tyrosine kinase), have been synthesized and tested <00BMCL2171>. 

The synthesis of 2-chloro-5,7-dihydro-6//-pyrrolo[2,3-rflpyri idine-6-one, 122, was accomplished by heating the alkenyl pyrimidine, 121, in acidic media (Equation 44) <2001TL999>. 

Perhaps the most unique synthesis of a pyrrolo[2,3-, pyrimidine arises from a completely acyclic precursor. Thus, 180, upon reaction with guanidine in basic media, produces both rings, although undoubtedly one ring is formed first in situ (Equation 68). Good yields of 181 were obtained <1995CPB256>. 

There are several unique methods that have been employed for the synthesis of pyrrolo[3,2-i7 pyrimidines. The following examples illustrate these approaches. 

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. 

In 1990 we initially became interested in the possibility of utilizing the acylative version of the Knorr pyrrole synthesis for the construction of pyrrolo[2,3-cf pyrimidines. Over the past 7 years this notion has been... 

At the conclusion, the total synthesis of rigidin (6) proceeded in nine steps and nearly 26% overall yield starting from 6-chlorouracil and ethyl 2,4-dimethoxybenzylglycinate. The utility of the acylative pyrrole annu-lation approach to a highly substituted pyrrolo[2,3-d]pyrimidine system was thus revealed. Next we chose to focus our attention on representative... 

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>. 

An unusual synthesis of a pyrrolo[2,3- ]pyrimidine without a functional group is based on the reaction of benzonitrile with A-methyl-2-pyrrolidone. These two compounds, when heated in the presence of sodium telluride, give low yields of 2,4-diphenyl-7-methylpyrrolo[2,3- ]pyrimidine <93JOC24l>. The yields could not be improved, thereby limiting the usefulness of the method. 

A few less traditional approaches to the synthesis of pyrrolo[2,3-<7]pyrimidines are worthy of note. Ketene 5,A-acetals (136) serve as convenient precursors to pyrrolopyrimidines which are reduced in the pyrrole ring (137) (Equation (47)). Heating compound (136) in a 1 2 ratio with arylisothiocyanates affords the dithio products (137 X = S) <83S225>, whilst similar treatment with arylisocyanates leads to the dioxo compounds (137 X = O) <85CPB4299>. 

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