- A One-step Synthesis of 2,4-Bis(sec-alkylamino)-6-halo-3-pyridinecarbonitriles
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The title compounds, e.g. 2a-c or 7, are obtained by reaction of malononitrile (1) with sec-alkylhalides/aluminium chloride (except the alkyl fluorides) at room temperature.From these the corresponding 2,4-bis(sec-alkylamino)pyridines may be conveniently prepared.With hydrogen bromide, 1 or its "dimer" 10 (R = H) 2,4-diamino-6-bromo-5-pyridinecarbonitrile (17) is formed.
- Metzger, Roland,Oberdoerfer, Juergen,Schwager, Carlos,Thielecke, Wilfried,Boldt, Peter
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p. 946 - 953
(2007/10/02)
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- 2,4-Diamino-5-benzylpyrimidines and Analogues as Antibacterial Agents. 3. C-benzylation of Aminopyridines with Phenolic Mannich Bases. Synthesis of 1- and 3-Deaza Analogues of Trimethoprim.
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Electrophilic substitution of 2,4-diaminopyridine by 2,6-disubstituted-4-phenols and by halogens (bromine and fluorine) produces 3-benzyl and 3-halo derivatives, plus a small amount of disubstitution at the 3,5 positions.Treatment of a 2,4-diamino-3-halopyridine with phenolic Mannich bases gives 5- and N-benzylation. 2,4-Diamino-3-bromo-5-(4-hydroxy-3,5-dimethoxybenzyl)pyridine was methylated on the phenolic group in good yield and dehalogenated to produce 3-deazatrimethoprim .This compound is about 300-fold less active as an inhibitor of Escherichia coli dihydrof olate reductase than is trimethoprim. 2,6-Diaminopyridine is very readily dibenzylated at the 3,5 positions, as well as on an amino group, by a phenolic Mannich base; use of a fourfold excess of the pyridine provided a 3-benzylated 2,6-diaminopyridine in 50percent yield; this was inactive as an inhibitor of dihydrofolate reductase at 10-4 M. 2-Amino- and 4-aminopyridines do not produce C-benzylated products under the conditions reported here.
- Rauckman, Barbara S.,Roth, Barbara
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p. 384 - 391
(2007/10/02)
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