A5064281993- Chemical Synthesis and Analysis
- Chemical Synthesis and Reactions
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Cyclopropane Reaction Mechanisms
- Catalytic C–H Functionalization Methods
- Coordination Chemistry and Organometallics
- Chemical Reaction Mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- HIV/AIDS drug development and treatment
- Oxidative Organic Chemistry Reactions
- Carbohydrate Chemistry and Synthesis
- Synthesis and Catalytic Reactions
- Catalytic Cross-Coupling Reactions
- Organophosphorus compounds synthesis
Bristol-Myers Squibb (United States)
2017-2022
The process development and the kilogram-scale synthesis of linrodostat (BMS-986205, 1) are described. features several highly efficient telescoped processes use Evans auxiliary to install a methyl-bearing stereocenter. target was prepared in 12 steps with 7 isolations an overall yield 31%.
The use of LiOH/H2O2 for cleavage Evans oxazolidinones is an essential but often overlooked part using these ubiquitous chiral auxiliaries in synthetic routes. These conditions were disclosed the literature more than 30 years ago and have found widespread with little change. During studies focused on synthesis a drug candidate, we discovered evolution oxygen under auxiliary. We find this phenomenon to be general tied fact that initially formed peracid not stable reaction conditions. rapidly...
The discovery, development, and optimization of an Ullmann–Goldberg–Buchwald coupling reaction is described. This complex process represents a key transformation in the development commercially viable synthesis HIV attachment inhibitor prodrug BMS-663068. In this reaction, high regioselectivities were obtained for 1,2,4-triazole 7-bromoazaindole, preparing BMS-626529, antepenultimate good yield quality. Key challenges associated with developing conditions copper-mediated include achieving...
The development of a convergent route to the NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. synthesis relies on key Miyaura borylation tandem Suzuki–Miyaura coupling between an iodoimidazole o-aminochloroarene, followed by acid-mediated cyclization afford aminoquinoline core. subsequent Boc cleavage regioselective acylation target compound. Two routes intermediate are presented, along with o-aminochloroarene via Negishi...
In the pharmaceutical industry, H2O2-mediated oxidation reactions are commonly used in chemical syntheses but they can also introduce unexpected safety hazards. Our labs recently reported on discovery of oxygen evolution during LiOH/H2O2-mediated cleavage Evans oxazolidinone. Faced with this previously hazard, authors, herein, report development and demonstration a methodology for safe scale-up O2-releasing reaction. It was found that O2 headspace could be controlled by combination N2...
The reaction optimization of an alkylation to enable the production penultimate intermediate HIV-attachment inhibitor candidate is described. To address challenges associated with reactivity and stability di-tert-butyl (chloromethyl) phosphate (2), poor solubility starting BMS-626529-Li salt (1), strategic selection Et4NI 325 mesh K2CO3 as additives, wet CH3CN solvent were required. An aqueous workup protocol was also developed selectively remove undesired N-6 isomer. final processing...