The palladium-catalyzed coupling of aryl and heteroaryl chlorides with primary amides under mild homogeneous reaction conditions is reported. Successful C−N coupling is enabled by the use of a unique "dual-base" system consisting of DBU and NaTFA, which serve as proton acceptor and halide scavenger, respectively, using low catalyst loadings (0.5 mol %) with readily available, air-stable palladium precatalysts. The DBU/NaTFA system also enables the room-temperature coupling of primary aryl amines with aryl chlorides and is tolerant of a variety of base-sensitive functional groups.
This paper describes a grassroots outreach program at Bristol Myers Squibb (BMS), organized by women chemists and chemical engineers, for women studying chemistry and chemical engineering. This effort supports the company's belief that excellence in creativity and innovation is enhanced when its scientists and engineers bring diverse experiences and backgrounds to the teams inventing and developing novel medicines. The in-person event includes seminars, poster sessions, lab tours, a networking lunch, and a discussion panel for students from local colleges and universities. These events were designed to expose students to potential careers in the pharmaceutical industry. We present data from 275 survey respondents out of the 354 participants from the past 7 years. The survey results were overwhelmingly positive and showed that the events were particularly impactful in (1) increasing an understanding of what chemists or chemical engineers do in the pharmaceutical industry, (2) presenting a broader view of academic options, (3) building higher confidence in the students' choice of major, and (4) fostering a sense of belonging and pride to be a woman in a STEM field. These events enhanced the company's ability to attract and hire top talent, while engaging current employees as role models for the next generation of women in STEM. We believe the program is an excellent model for other companies, industries, and professional societies to attract talented students from underrepresented groups to STEM fields.
The
development of a convergent route to the NLRP3 (nucleotide-binding
domain and leucine-rich repeat-containing protein 3) agonist BMS-986299
is reported. The synthesis relies on a key Miyaura borylation and
a tandem Suzuki–Miyaura coupling between an iodoimidazole and
an o-aminochloroarene, followed by acid-mediated
cyclization to afford the aminoquinoline core. The subsequent Boc
cleavage and regioselective acylation afford the target compound.
Two routes to the iodoimidazole intermediate are presented, along
with the synthesis of the o-aminochloroarene via
Negishi coupling. The convergent six-step route leads to an 80% reduction
in process mass intensity compared to the linear enabling synthesis.
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