1. Improved synthesis of sterically encumbered heteroaromatic biaryls from aromatic β-keto esters
- Author
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Ehesan U. Sharif, Jay P. Powers, Nicholas S. Chan, Dillon H. Miles, Manmohan Reddy Leleti, and Brandon Reid Rosen
- Subjects
Steric effects ,010405 organic chemistry ,Aryl ,Organic Chemistry ,010402 general chemistry ,Condensation reaction ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,0104 chemical sciences ,chemistry.chemical_compound ,Column chromatography ,chemistry ,Drug Discovery ,Guanidine - Abstract
A protocol for the synthesis of hindered 4-aryl 2-aminopyrimidines from β–keto esters is described. The process employs trifluoroethanol as an essential additive to promote the guanidine condensation reaction, enabling the synthesis of 25 aryl- and heteroaryl substituted aminopyrimidines in good yields and high purities with no column chromatography. The conditions described herein are readily scalable and have been employed in the large-scale synthesis of the clinical A2a/A2bR antagonist AB928.
- Published
- 2020
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