Solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives via dithiocarbazate linker.
A general method is reported for the parallel solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives based on the cyclization of polymer-bound dithiocarbazate 3 with various electrophiles, such as 3-ethoxyacrylonitriles 8 and cyanocarboimidates 9. The polymer-bound dithiocarbazate 3, produced by nucleophilic reaction with carbon disulfide and Fmoc-hydrazine on the Merrifield resin, served as the key intermediate for subsequent heterocycle diversification. Further nucleophilic substitution on these polymer-bound 5-amino-1-dithiocarboxypyrazoles 4 and 1,2,4-triazoles 6 with various amines under thermal cleavage condition produced the desired 5-amino-1-(substituted thiocarbamoyl)pyrazoles 5 and 1,2,4-triazoles 7. The progress of reactions could be monitored as polymer-bound intermediates by ATR-FTIR spectroscopy on single bead. The final compounds, obtained in good four-step overall yields and high purities upon cleavage from the resins, were characterized by LC/MS, 1H NMR, and 13C NMR spectroscopy.
Hwang
Jong Yeon
JY
Medicinal Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yusung-gu, Daejeon 305-600, Korea.
Choi
Hyung-Sub
HS
Lee
Duck-Hyung
DH
Yoo
Sung-Eun
SE
Gong
Young-Dae
YD
D000586:Amination; D001393:Azoles / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006834:Hydrazines / Q000737:chemistry*; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
D001393:Azoles; D003432:Cross-Linking Reagents; D006834:Hydrazines; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; D013844:Thiazoles; C031280:pyrazole; C010877:carbazic acid