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Novel synthetic route for 5‐substituted 6‐arylmethylluracils from 2,4,6‐trichloropyrimidines
Author(s) -
Loksha Yasser M.
Publication year - 2009
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.239
Subject(s) - chemistry , sodium methoxide , acetonitrile , aryl , halogenation , iodide , methyl iodide , hydrolysis , medicinal chemistry , bromide , cyanide , alkylation , nitrile , cyanoacetamide , trimethylsilyl cyanide , sodium iodide , methanol , organic chemistry , catalysis , alkyl
Treatment of 2,4,6‐trichloropyrimidines ( 1a , 1b ) with the sodium salt of benzyl cyanide derivatives ( 2a , 2b ) afforded 5‐substituted 4‐aryl(cyanomethyl)‐2,6‐dichloropyrimidines ( 3a , 3b , 3c , 3d , 3e , 3f ). Compounds 3a , 3b were alkylated with methyl iodide to furnish 4‐(1‐aryl‐1‐cyanoethyl)‐2,6‐dichloropyrimidines ( 4a , 4b ). Compounds 3a , 3b , 3c , 3d , 3e , 3f and 4a , 4b were hydrolyzed with concentrated hydrochloric acid to afford 5‐substituted 6‐arylalkyluracils 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h . 5‐Bromo‐6‐arymethylluracils ( 6a , 6b , 6c , 6d ) were synthesized by bromination of 6‐arylmethylluracils ( 5a , 5b , 5c , 5d ) with N ‐bromosuccinimide (NBS). Refluxing 2‐(2,6‐dichloro‐5‐ethylpyrimidin‐4‐yl)‐2‐(3,5‐dimethylphenyl)acetonitrile ( 3f ) with sodium methoxide followed by oxidation afforded (3,5‐dimethylphenyl)(5‐ethyl‐2,6‐dimethoxypyrimidin‐4‐yl)methanone ( 7 ). Addition of methylmagnesium bromide to compound 7 gave the tertiary alcohol derivative 8 which was fluorinated by diethylaminosulfurtrifluoride and deprotected by trimethylsilyl iodide to furnish 6‐(1‐(3,5‐dimethylphenyl)‐1‐fluoroethyl)‐5‐ethylpyrimidine‐2,4(1 H ,3 H )‐dione ( 12 ). J. Heterocyclic Chem., (2009).