Manufacturing Process Development of Tegoprazan as a Potassium-Competitive Acid Blocker (P-CAB)

Tegoprazan, a selective potassium-competitive acid blocker, was approved in 2018 in the Republic of Korea for the treatment of gastroesophageal reflux disease (GERD), erosive esophagitis (EE), and nonerosive reflux disease (NERD). The complexity of tegoprazan, which contains a 4,6-disubstituted 1H-benzo[d]imidazole core and a chiral chromanol moiety, makes it a challenging molecule to prepare on a commercial scale. An efficient and economical route of the key intermediates and a much improved end-game for tegoprazan were developed

Catalyst-Controlled C–H Allylation and Annulation of 2‑Aryl Quinazolinones with 2‑Methylidene Cyclic Carbonate

The site-selective modification of quinazolinone as a privileged bicyclic N-heterocycle is an attractive topic in medicinal chemistry and material science. We herein report the ruthenium­(II)-catalyzed C–H allylation of 2-aryl quinazolinones with 2-methylidene cyclic carbonate. In addition, tandem C–H allylation and annulation are achieved under rhodium­(III) catalysis, resulting in the formation of tetracyclic quinazolinones including a tertiary carbon center. Post-transformations of the synthesized products demonstrate the potential of the developed methodology. A series of mechanistic investigations were also performed

Catalyst-Controlled C–H Allylation and Annulation of 2‑Aryl Quinazolinones with 2‑Methylidene Cyclic Carbonate

The site-selective modification of quinazolinone as a privileged bicyclic N-heterocycle is an attractive topic in medicinal chemistry and material science. We herein report the ruthenium­(II)-catalyzed C–H allylation of 2-aryl quinazolinones with 2-methylidene cyclic carbonate. In addition, tandem C–H allylation and annulation are achieved under rhodium­(III) catalysis, resulting in the formation of tetracyclic quinazolinones including a tertiary carbon center. Post-transformations of the synthesized products demonstrate the potential of the developed methodology. A series of mechanistic investigations were also performed