Parallel iterative solution-phase synthesis of 5-amino-1-aryl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid amide derivatives

Tetrahedron Letters

Volumn 44, Issue 8, 2003, Pages 1675-1678

  Brodbeck, Bernd ^a   Püllmann, Bernd ^a   Schmitt, Sébastien ^a   Nettekoven, Matthias ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Combinatorial chemistry; Iterative solution phase chemistry; Lead optimisation; N amination; Triazolo 1,5 a pyridine derivatives

Indexed keywords

2,6 DIAMINOPYRIDINE 4 CARBOXYLIC ACID METHYL ESTER; ALDEHYDE; AMIDE; CARBOXYLIC ACID DERIVATIVE; ESTER DERIVATIVE; PYRIDINE; PYRIDINE DERIVATIVE; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; COMBINATORIAL LIBRARY; CYCLIZATION; DRUG ACTIVITY; IN VITRO STUDY; MOLECULAR MODEL; OXIDATION; PROCESS OPTIMIZATION; SYNTHESIS;

EID: 0037450511     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00062-5     Document Type: Article

References (18)

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9. 2: C, 50.30; H, 5.43; N, 25.14. Found: C, 50.27; H, 5.26; N, 24.11.
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12. For a more detailed description of the procedure that led to the amine starting material selection for the respective iterative cycle, see: Schneider, G.; Nettekoven, M. J. Comb. Chem. 2003, in press.
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16. General procedure for the synthesis of 1: To a solution of 0.44 mmol amine in 0.5 ml dioxane was added 0.5 ml methylaluminoxane (10% in toluene) (use of trimethylaluminium instead of methylauminoxane gave comparable results) and the mixture was stirred for 1 h at room temperature. 0.11 mmol [1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid methyl ester in 1 ml dioxane was added and the mixture was heated to 90°C for 72 h. After addition of 0.4 ml 1N HCl the mixture was evaporated to dryness and the residue was taken up in 1.5 ml DMSO, filtered, and the title compound was isolated by reversed-phase HPLC eluting with a water/acetonitrile gradient.
17. 2).
18. For a more detailed description of workflow procedures and automation technology utilised for this synthetic array, see: Nettekoven M., Thomas A.W. Curr. Med. Chem. 9:2002;2179-2190.