- Utilizing Native Directing Groups: Mechanistic Understanding of a Direct Arylation Leads to Formation of Tetracyclic Heterocycles via Tandem Intermolecular, Intramolecular C-H Activation
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A mechanistic study on a direct arylation using a native picolylamine directing group is reported. Kinetic studies determined the concentration dependence of substrates and catalysts, as well as catalyst degradation, which led to the development of a new set of reaction conditions capable of affording a robust kinetic profile. During reaction optimization, a small impurity was observed, which was determined to be a dual C-H activation product. A second set of conditions were found to flip the selectivity of the C-H activation to form this tetracycle in high yield. A catalytic cycle is proposed for the intermolecular/intramolecular C-H activation pathway.
- Wisniewski, Steven R.,Savage, Scott A.,Romero, Evan O.,Eastgate, Martin D.,Tan, Yichen,Simmons, Eric M.,Plata, R. Erik,Sowa, John R.,Blackmond, Donna G.
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- Utilizing Native Directing Groups: Synthesis of a Selective IKur Inhibitor, BMS-919373, via a Regioselective C-H Arylation
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BMS-919373 is a highly functionalized quinazoline under investigation as a selective, potent IKur current blocker. By utilizing the aminomethylpyridine side chain at C-4, a selective C-H functionalization at C-5 was invented, enabling the effic
- Wisniewski, Steven R.,Stevens, Jason M.,Yu, Miao,Fraunhoffer, Kenneth J.,Romero, Evan O.,Savage, Scott A.
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p. 4704 - 4714
(2019/04/30)
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- QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS
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A compound of formula (I) wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.
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Page/Page column 220-221
(2011/04/14)
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