A novel route to the synthesis of 3-pyridine carboxaldehydes by Vilsmeier reagent
2-Chloro-5-aryl-3-pyridine carboxaldehydes are obtained by Vilsmeier reaction of 4-aryl-3-buten-2-one oxime. The suspected intermediate N-(2- arylethenyl)acetamides also give the same 2-chloro-5-aryl-3-pyridine carboxaldehydes under identical reaction condition.
We report the identification of a novel biaryl template for H+/K+ ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving activity. Herein we present our work optimising the potency of the molecule through modifications and substitutions to each of the ring systems. In particular sub-micromolar potency is achieved with (4b) presumably through a proposed intramolecular hydrogen bond that ensures the required imidazole basic centre is appropriately located.
Garton, Neil,Bailey, Nick,Bamford, Mark,Demont, Emmanuel,Farre-Gutierrez, Irene,Hutley, Gail,Bravi, Gianpaolo,Pickering, Paula
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p. 1049 - 1054
(2010/06/12)
Facile and selective synthesis of chloronicotinaldehydes by the Vilsmeier reaction
Eleven enamides were prepared by adopting different procedures. The various enamides prepared were subjected to Vilsmeier reaction using (i) POCl3/DMF; (ii) diphosgene/DMF; (iii) triphosgene/DMF leading to the formation of various multisubstituted chloronicotinaldehydes. Studies carried out indicate that Vilsmeier reagent concentration and the replacement of POCl3 by diphosgene or triphosgene, provides excellent selectivity and higher yields. Under modified reaction conditions one can get only chloronicotinaldehydes and not the chloropyridines as products. The various advantages in using diphosgene and triphosgene are illustrated. The mechanism of formation of chloronicotinaldehyde was discussed.