Scalable Synthesis of β-Lactamase Inhibitor QPX7728 by Sequential Nickel-Catalyzed Boron Insertion into a Benzofuran Substrate and Enantioselective Cyclopropanation of the Resulting Vinylboronate
We report the scalable, high-yielding, and highly selective synthesis of the β-lactamase inhibitor QPX7728 featuring two key synthetic steps: nickel-catalyzed boron insertion of benzofuran 1 followed by enantioselective cyclopropanation of the resulting cyclic vinylboronate 2. The identification of the key reagents (catalyst and chiral auxiliary) for both steps relied on the use of high-throughput experimentation. Further optimization allowed for the cost-effective and scalable production of QPX7728.
Boyer, Serge H.,Gonzalez-De-Castro, Angela,Dielemans, J.A. Hubertus,Lefort, Laurent,Zhu, Zuolin,Gnahn, Matthias,Sch?rghuber, Julia,Steinhofer, Stefan,De Vries, André H. M.,Hecker, Scott J.
(2021/10/01)
PHARMACEUTICAL COMPOSITION ADMINISTERED IN COMBINATION WITH SUBSTITUTED DIHYDROPYRROLOPYRAZOLE COMPOUND AND IMMUNOTHERAPEUTIC AGENT
The present invention provides a pharmaceutical composition comprising a compound represented by the formula (I) or a pharmacologically acceptable salt thereof wherein two R moieties each independently are a C1-3 alkyl group or are groups bonded to each other to form a C2-5 alkylene group; A is an optionally substituted C6-10 aryl group or an optionally substituted heteroaryl group; and R1, R2 and R3 each independently are an optionally substituted linear or branched C1-4 alkyl group, wherein the pharmaceutical composition is administered in combination with an immunotherapeutic agent.
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Paragraph 0134-0136
(2020/09/17)
BORONIC ACID DERIVATIVES AND SYNTHESIS THEREOF
Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the method of use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents, for example, β-lactamase inhibitors (BLIs).
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(2019/05/06)
SUBSTITUTED DIHYDROPYRROLOPYRAZOLE DERIVATIVE
The present invention provides a compound represented by the general formula (Ia) or a pharmacologically acceptable salt thereof. In the general formula (Ia), two R moieties each independently represent a C1-3 alkyl group or the like; and R1, R2 and R3 each independently represent an optionally substituted linear or branched C1-4 alkyl group.
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Paragraph 1159; 1160; 1161; 1162; 1163
(2018/07/29)
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