Structural studies on bioactive compounds. Part 27. Chemistry of the immunomodulatory agent bropirimine.
The 2-amino-6-phenylpyrimidin-4(3H)-ones bropirimine (1) and the debrominated analogue (4) undergo electrophilic nitration and sulphonation in the meta-position of the 6-phenyl group in strongly acidic conditions. Subsequent electrophilic substitutions take place in the 5-position of the pyrimidine ring, if vacant. Rearrangement of the 2-nitramino-6-phenyl-pyrimidines (22) and (23) furnishes the 2-amino-6-(3-nitrophenyl)pyrimidines (9) and (18), respectively. Nucleophilic substitutions, in contrast, occur readily in the pyrimidine 2-, 4- and 6-positions. Debromination of bropirimine by hydrazine hydrate can be rationalized by invoking an initial attack by the nucleophile at the electron-deficient pyrimidine 6-position. The reactive 4-chloro group in 5-bromo-4-chloro-2-formylamino-6-phenylpyrimidine (25) can be displaced with a range of nucleophiles (azide ion, ethanol, hydrazine, and primary and secondary aliphatic amines), without loss of the bromo substituent.
Stevens
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Cancer Research Laboratories, University of Nottingham, UK.
Baig
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Gate
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Wheelhouse
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D000276:Adjuvants, Immunologic / Q000737:chemistry*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared
D000276:Adjuvants, Immunologic; D003596:Cytosine; C033560:bropirimine