A5013941438- Catalytic Cross-Coupling Reactions
- Chemical Synthesis and Analysis
- Radical Photochemical Reactions
- Catalytic C–H Functionalization Methods
- Coordination Chemistry and Organometallics
- Analytical Chemistry and Chromatography
- Synthesis and Catalytic Reactions
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Fluorine in Organic Chemistry
- Computational Drug Discovery Methods
- Free Radicals and Antioxidants
- Asymmetric Hydrogenation and Catalysis
- Advanced Synthetic Organic Chemistry
- Microfluidic and Capillary Electrophoresis Applications
- Synthesis and Biological Evaluation
- Synthesis of β-Lactam Compounds
- Mass Spectrometry Techniques and Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Heart Failure Treatment and Management
- Marine Sponges and Natural Products
- Pharmacogenetics and Drug Metabolism
- Protein purification and stability
- Enterobacteriaceae and Cronobacter Research
- NMR spectroscopy and applications
University of British Columbia
2017-2022
Vancouver Biotech (Canada)
2017-2020
University of Calgary
2015-2017
Calgary Laboratory Services
2017
Public Health Agency of Canada
2014
Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products formed excellent yield enantioselectivity no observed bis-acylation. A data-science-driven approach substrate scope evaluation was coupled high throughput experimentation (HTE) facilitate statistical modeling order inform mechanistic studies....
Automated sampling and in-line dilution allows both homogeneous heterogeneous reactions to be easily profiled by real-time HPLC-MS.
Detailed kinetic analysis for the Cu(I)-catalyzed Kinugasa reaction forming β-lactams has revealed an anomalous overall zero-order profile, due to opposing positive and negative orders in nitrone alkyne, respectively. Furthermore, displays a second-order dependence on catalyst, confirming critical involvement of postulated bis-Cu complex. Finally, progress multiple byproducts allowed new mechanism, involving common ketene intermediate be delineated. Our results demonstrate that β-lactam...
Abstract Ring walking is an important mechanistic phenomenon leveraged in many catalytic C-C bond forming reactions. However, ring has been scarcely studied under Buchwald-Hartwig amination conditions despite the importance of such transformations. An in-depth study presented focussing on ligand effects behavior. The ability palladium catalysts to promote or inhibit strongly influenced by chelating nature ligand. In stark contrast, resting state catalyst had no impact Furthermore, complexity...
Herein, we report a new one-pot sequential method for SO2F2-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that acid activation proceeds via the anhydride, which is then converted to corresponding fluoride. Tetrabutylammonium chloride or bromide accelerate formation of Optimized halide-accelerated conditions were used synthesize fluorides in 30-80% yields, and esters, amides, thioesters 72-96% yields without reoptimization each...
The development of a scalable continuous flow process to synthesize densely functionalized quinazoline organozinc intermediate toward KRAS G12C inhibitor divarasib (GDC-6036) is reported herein. A traditional cryogenic batch metalation was initially employed, but instability the organomagnesium species above −60 °C presented logistical roadblock, with limited flexibility for its implementation as manufacturing scale increased. An investigation underlying component reaction kinetics in mode...
The mechanisms for the three- and four-component variants of Castagnoli–Cushman reaction (CCR) have been investigated. A series crossover experiments were conducted to probe structure reactivity known amide-acid intermediates CCR (3CR 4CR, respectively). Control paired with in situ monitoring infrared spectroscopy 4CR align a mechanism which amide-acids derived from maleic anhydride can reversibly form free amine cyclic anhydride. Although this equilibrium is unfavorable, aldehyde present...
Herein, we describe the development of two continuous manufacturing processes for synthesis 6-chloro-1H-pyrazolo[3,4-b]pyrazine, which is a key intermediate en route to SHP2 inhibitor GDC-1971 (migoprotafib). The reaction sequence starts with plug-flow metalation/formylation readily available 2,6-dichloropyrazine using i-Pr2NMgCl·LiCl (MgDA) as base, whereupon resulting unstable heteroaryl aldehyde isolated its easier-to-handle and bench-stable bisulfite adduct. ensuing cyclization step...
Obtaining data-dense reaction profiles for reactions performed under an inert atmosphere remains a significant challenge obfuscating mechanistic analysis. To this end, we have developed monitoring platform capable of automated sampling and online HPLC analysis to generate temporal from within glovebox. The device allows facile progress aid in studies air-sensitive chemical transformations. has demonstrated high reproducibility regarding sample mixing, dilution, delivery, We employed the...
The crystallization-induced diastereomer transformation of a precursor to navoximod was investigated using online HPLC and optimized with inline racemization.
Carvedilol is a widely prescribed drug for the treatment of heart failure and prevention associated ventricular arrhythmias.
Palladium-catalyzed cross-couplings remain among the most robust methodologies to form carbon-carbon and carbon-heteroatom bonds. In particular, carbon-nitrogen (C-N) couplings (Buchwald-Hartwig aminations) find widespread use in fine chemicals industries. The of base these reactions is critical for catalyst activation proton sequestration. Base selection also plays an important role process design, as strongly basic conditions can impact sensitive stereocenters result erosion stereochemical...
We have developed a reaction monitoring method which provides quantitative information through exchange, transmetalation (TM), and cross-coupling for Negishi reaction. Online HPLC ReactIR were used as orthogonal techniques to corroborate time-course data each step. Excellent agreement between the two was observed magnesium/bromine exchange. Quantitative regarding TM gathered via novel, inline quenching technique facilitated by online HPLC. Quenching aliquots with electrophile...
Telescoped synthesis enabled by reaction monitoring.
Methods to access chiral sulfur (VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products formed excellent yield enantioselectivity no observed bis-acylation. A data science-driven approach substrate scope evaluation was coupled high throughput experimentation (HTE) facilitate statistical modeling order inform mechanistic studies....
We report a technique for monitoring the drying of drug substances in agitated filter-dryers. Online gas chromatography (GC) was leveraged to perform unattended sampling headspace filter-dryer throughout drying. To validate technique, we monitored sodium naproxen an using ternary solvent system consisting methyl tert-butyl ether, acetonitrile, and isopropyl acetate. A curve each generated with frequency <6 min per injection. Physical disturbances cake that occurred were observed as spikes...
Abstract Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique with the ability to acquire both quantitative and structurally insightful data for multiple components in test sample. This makes NMR desirable tool understand, monitor, optimize chemical transformations. While (qNMR) approaches relying on internal standards are well‐established, using an absolute external calibration scheme beneficial reaction monitoring as overlap complications from added reference...
We have developed a reaction monitoring platform capable of automated sampling and online HPLC analysis to generate temporal profiles for reactions performed from within glovebox. The device allows facile progress aid in mechanistic studies air-sensitive chemical transformations. has demonstrated high reproducibility regarding sample mixing, dilution, delivery, analysis. employed the acquire series Buchwald-Hartwig aminations. Parallel coupling using iodobenzene bromobenzene both exhibit...
We have developed a reaction monitoring platform capable of automated sampling and online HPLC analysis to generate temporal profiles for reactions performed from within glovebox. The device allows facile progress aid in mechanistic studies air-sensitive chemical transformations. has demonstrated high reproducibility regarding sample mixing, dilution, delivery, analysis. employed the acquire series Buchwald-Hartwig aminations. Parallel coupling using iodobenzene bromobenzene both exhibit...