Facile, Regioselective Syntheses of N-Alkylated 2, 3-Diaminopyridines and Imidazo[4, 5-b]pyridines

Journal of Organic Chemistry

Volumn 60, Issue 4, 1995, Pages 960-965

  Khanna, Ish K ^a,b   Weier, Richard M ^a,b   Lentz, Kirk T ^a,b   Swenton, Lydia ^a,b   Lankin, David C ^a,b  

^a PFIZER INC   (United States)

^b Department of Physical Methodology ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMIDAZO[4,5 B]PYRIDINE DERIVATIVE; PYRIDINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0028812845     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo00109a029     Document Type: Article

References (17)

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3. Weier, R. M.; Khanna, I. K.; Stealey, M. A.; Julien, J. (Searle). U. S. Pat. 5 262 426, 1993.
4. Weier, R. M.; Khanna, I. K.; Lentz, K.; Stealey, M. A.; Julien, J. (Searle) U. S. Pat. 5 359 073, 1994.
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10. Of the regioselective syntheses of AT-alkylated imidazo[4, 5-6]-pyridines and 2, 3-diaminopyridines reported in literature, the preparation of 2- (alkylamino)-3-aminopyridines seems the simplest as these can be easily prepared by starting with 2-chloro-3-nitropyridines. Robison, M. M.; Switzerland, R.; Finch, N. (Ciba-Geigy); U. S. Pat. 3 719 683, 1973; see also ref 5.
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15. Substituted benzaldehydes 10 and 16, the intermediates used in our PAF program, were initially prepared from the corresponding benzyl bromides by direct oxidation using trimethylamine N-oxide in DMSO. However, this transformation could not be scaled up very well and we routinely preferred to use the three-step sequence involving (a) displacement of the substituted benzyl bromide with acetate (NaOAc, DMF) (b) hydrolysis (aqueous K2CO3) of the ester, and (c) oxidation (PCC) to the desired aldehyde. The synthesis of substituted benzyl bromides has been reported: Khanna, I. K.; Nosal, R.; Weier, R. M. (Searle). U. S. Patent 4 914 108 and 5 019 581; Chem. Abstr. 1990, 112, 235299z.
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