Synthesis toward CRHR1 Antagonists through 2,7-Dimethylpyrazolo1,5-alpha1,3,5triazin-4(3H)-one C-H Arylation

摘要

A novel synthetic protocol for 8-aryl substituted pyrazolo1,5-alpha 1,3,5triazin-4(3H)-ones was developed employing Pd-catalyzed C-H arylation. The reaction yield was influenced by the presence of a phosphine ligand, pivalic acid, and base selection. With the use of 5-10 mol catalyst, reactions of 2 with p- or m-substituted aryl bromides proceeded in moderate to good yields. Lower yields were observed with o-substituted aryl bromides. Using this method a precursor for MJL1-109-2, a known nonpeptide CRHR-1 antagonist, was successfully synthesized.