887626-20-2Relevant articles and documents
P2X7 MODULATORS
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Paragraph 0126; 0180; 0181, (2014/09/30)
The present invention is directed to a compound of Formula (I) and to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.
Metal-bearing and trifluoromethyl-substituted pyrimidines: Generation and functionalization
Schlosser, Manfred,Lefebvre, Olivier,Ondi, Levente
, p. 1593 - 1598 (2007/10/03)
5-Pyrimidyllithium species are fairly stable when the metal is flanked by two electron-withdrawing substituents such as trifluoromethyl and chlorine or bromine. Thus, the corresponding 5-carboxylic acids are produced in high yields from 4,5-dibromo-6-(trifluoromethyl)pyrimidine and 5-bromo-4-chloro-6- (trifluoromethyl)pyrimidine upon halogen/metal permutation accomplished with isopropylmagnesium chloride or butyllithium followed by carboxylation. Satisfactory or excellent yields of 5-carboxylic acids are equally obtained when 4-chloro-, 2,4-dichloro- and 2,4-dibromo-6-(trifluoromethyl)pyrimidine are deprotonated with lithium diisopropylamide before being allowed to react with dry ice. In contrast, consecutive treatment of 2-bromo-4-(trifluoromethyl) pyrimidine and 2-chloro-5-iodo-4-(trifluoromethyl)pyrimidine with butyllithium affords the expected carboxylic acids in only poor yields and not even trace amounts of acid were detected when 4-bromo-6-(trifluoromethyl)pyrimidine served as the substrate. The formation of bipyrimidines, emerging from either one of two competing mechanistic pathways, is a permanently menacing side reaction. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
