192653-35-3Relevant academic research and scientific papers
An Improved Synthesis of 7-Substituted Pyrrolo[3,2-d]pyrimidines
Elliott, Arthur J.,Morris Jr., Philip E.,Petty, Sandra L.,Williams, Carl H.
, p. 8071 - 8075 (2007/10/03)
Base (NaOMe)-catalyzed condensation of 3,3-dimethoxypropionitrile with aldehydes followed by hydrolysis with 6 N HCl gives the unsaturated cyano aldehydes 5. Catalytic reduction of the double bond followed by reaction with diethyl aminomalonate affords the enamines 7, which cyclize to the aminopyrroles 2 on treatment with NaOMe. While the amino group in 2 is unreactive toward many guanylating reagents, acid (AcOH)-catalyzed guanylation occurs easily with 10 to give 12 along with methyl mercaptan as a byproduct. Subsequent facile removal of the carbamate groups and ring closure to the pyrrolo[3,2-d]pyrimidine ring system occurs on treatment with base. The use of HgCl2 in place of AcOH ties up the mercaptan and eliminates the odor problem. For larger scale reactions where the mercaptan odor and the use of Hg salts are undesirable, the use of the methoxy analogue 11 is preferred. Using this procedure, benzaldehyde has been converted to the 7-(phenylmethyl)pyrrolo[3,2-d]pyrimidine (1a), a potent inhibitor of the enzyme purine nucleoside phosphorylase, in 31% overall yield with only three isolation steps.
Process for the preparation of 9-deazaguanine derivatives
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, (2008/06/13)
Derivatives of 9-deazaguanine are prepared by reacting an aldehyde or ketone with a dialkylaminomalonate to form the corresponding enamine. The enamine is then reacted with a base to form a cyclic pyrrole. The cyclic pyrrole is reacted with an urea compound to provide a protected guanidino compound. The guanidino is converted to the desired 9-deazaguanine derivative by reacting with trifluoracetic acid or with an alkoxide or hydroxide followed by neutralization with an acid.
