Application of Solution-Phase Parallel Synthesis to Preparation of Trisubstituted 1,2,4-Triazoles

Journal of Combinatorial Chemistry

Volumn 6, Issue 1, 2004, Pages 35-37

  Martin, Scott W ^a   Romine, Jeffrey L ^a   Chen, Ling ^a   Mattson, Gail ^a,b   Antal Zimanyi, Ildiko A ^a,c   Poindexter, Graham S ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b Neuroscience Biology   (United States)

^c Department of Metabolic Research ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIAZOLE DERIVATIVE; AMINE; HYDRAZIDE; NEUROPEPTIDE Y RECEPTOR ANTAGONIST; NITRILE; NITROGEN;

ALKYLATION; ARTICLE; AUTOMATION; CYCLIZATION; DRUG SCREENING; HEATING; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IC 50; ISOMER; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PROTON NUCLEAR MAGNETIC RESONANCE; PURIFICATION; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SYNTHESIS;

EID: 0942289839     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc034018s     Document Type: Article

References (21)

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10. Triethylamine as co-solvent was necessary to suppress formation of a trisubstituted 4-aminotriazole resulting from combination of two acid hydrazides into one imidate.
11. Vac-elute was fitted with 6 x 75-mL syringe cartridges charged with silica gel to 1/3 volume. Details are available in the Supporting Information.
12. Felder, R. JALA 1999, 4, 46-47.
13. For alkylation of a triazole via Mitsunobu reaction, see: Carlsen, H. J. ; Gautun, O. R. Acta Chem. Scand. 1990, 44, 485-488. Carlsen, H. J.; Jorgensen, K. B. J. Heterocycl. Chem. 1997, 34, 797-806.
14. For alkylation of a triazole via Mitsunobu reaction, see: Carlsen, H. J. ; Gautun, O. R. Acta Chem. Scand. 1990, 44, 485-488. Carlsen, H. J.; Jorgensen, K. B. J. Heterocycl. Chem. 1997, 34, 797-806.
15. Our success rates ranged from 45 to 72%. For an example of Mitsunobu reaction under automated conditions, see: Krchák, V.; Flegelová, Z.; Weichsel, A. S.; Lebl, M. Tetrahedron Lett. 1995, 36, 6193-6196.
16. For another example of parallel solution phase work relying on preparative HPLC, see: Tommasi, R. A.; Whaley, L. W.; Marepalli, H. R. J. Comb. Chem. 2000, 2, 447-449.
17. In some cases, samples were found to be contaminated with the reduction product of DIAD (only evident by 1H NMR).
18. Larger protecting groups than acetaldehyde on the hydrazide gave predominantly O-alkylation products (benzaldehyde, acetone, propionaldehyde).
19. We do not intend to imply that band 1 for all products is the same isomer as compound 1, but once unequivocally established, 1H NMR data of 1 vs 2 could be used in elucidation of other isomers.
20. The major product of the condensation reaction was the intermediate acylated hydrazide (>50%) where hydrolysis of the thioamide to amide product was observed instead of cyclization.
21. This work was presented in part at the 57th Southwest Regional American Chemical Society Meeting, San Antonio, TX, Oct 2001, by Romine, J. L., Martin, S. W., Chen, L., Poindexter, G. S., Antal-Zimanyi, I., and Matson, G.