Metathesis Reactions of Pyrazolotriazinones Generate Dynamic Combinatorial Libraries

Abstract

[reaction: see text] Reversible metathesis reactions of pyrazolotriazinones and aliphatic aldehydes or ketones proceed in aqueous, phosphate-buffered media at pH 4 and 40-60 degrees C to generate thermodynamically controlled mixtures of heterocycles.

Dynamic Combinatorial Chemistry

“…178 The exchange reaction proceeds in water at pH 4, and equilibrium was reached in 3 days at 40°C (1 mM concentration for each starting material). Exchange could be stopped by raising the pH to 7, allowing for the isolation of selected library members.…”

Synthesis and biological evaluation of new pyrazol-4-ylpyrimidine derivatives as potential ROS1 kinase inhibitors

“…pyridin-3-yl)pyrimidin-4-yl)ethan-1-one(14) Flash column chromatography was carried out using ethyl acetate to give the title compound in the enol form. Yield: (0.6 g, 93%); mp 125e126 C;1 H NMR (CDCl 3 ) d 2.00 (p, J ¼ 6.0, 12.4 Hz, 2H), 3.42 (s, 3H), 3.…”

Dynamic Combinatorial Chemistry: An Introduction

“…Another process mechanistically related to imine exchange is the dynamic production of pyrazolotriazinones reported in 2005 by Wipf and coworkers [ 29 ]. After first verifying that reaction of either 16 or 17 with equimolar quantities of isobutyraldehyde and hydrocinnamaldehyde at 40 ˚ C in water (pH 4.0) resulted in the same 3:7 mixture of 16 and 17 at equilibrium ( Fig.…”