A5077984658- Innovative Microfluidic and Catalytic Techniques Innovation
- Energetic Materials and Combustion
- Thermal and Kinetic Analysis
- Chemistry and Chemical Engineering
- Risk and Safety Analysis
- Chemical Safety and Risk Management
- Biochemical and Molecular Research
- Asymmetric Hydrogenation and Catalysis
- Synthetic Organic Chemistry Methods
- Antimicrobial agents and applications
- Chemical Reaction Mechanisms
- Process Optimization and Integration
- Chemical Synthesis and Analysis
- Synthesis and biological activity
- Chemical Synthesis and Reactions
- Catalysis and Hydrodesulfurization Studies
- Peptidase Inhibition and Analysis
- Asymmetric Synthesis and Catalysis
- Cholinesterase and Neurodegenerative Diseases
- SARS-CoV-2 and COVID-19 Research
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Click Chemistry and Applications
- Pesticide Exposure and Toxicity
- CAR-T cell therapy research
- Protein purification and stability
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2024
Pearl River Community College
2010
1,1′-Carbonyldiimidazole was found to induce the formation of a variety 3,4-disubstituted 1,2,5-oxadiazoles (furazans) from corresponding bisoximes at ambient temperature. This method enables these inherently energetic compounds be prepared temperatures well below their decomposition points and with improved functional group compatibility relative prior methods. Conditions were developed that allowed for first high-yielding synthesis chlorofurazans amino counterparts, enabling mild synthetic...
Our company has developed a robust and scalable process to synthesize an amino alcohol tosylate salt, penultimate intermediate in the synthesis of nemtabrutinib. A key reaction this synthetic sequence is reductive acetal ring opening using boron trifluoride diethyl etherate as Lewis acid triethylsilane reducing agent. Detailed mechanistic inquisition revealed that presence sulfolane, reduced by generate diborane active reductant. Diborane poses many safety hazards; it highly reactive,...
Azidoethyl phenyl sulfide, a readily accessible and reasonably stable synthon for ethyl azide with acceptable thermal safety properties, was investigated in preliminary design space evaluation of [3 + 2]-cycloaddition cyanoacetamide under continuous-flow conditions the Syrris AFRICA flow reactor.
The manufacturing route toward gefapixant citrate generates a trace amount of cyanide as byproduct reaction employing the reagent chloroacetonitrile. In development control strategy, conventional process and analytical approaches fell short because challenges incompatibilities with matrices waste streams. To overcome these, we identified adapted specific procedures for control. Our strategy ensured safety patients, operators, management.
The development of a stereospecific synthesis IDO1-selective inhibitor is described. synthetic strategy toward enabling early discovery efforts along with additional findings pertaining to process safety that limited scalability are outlined. A convergent approach supported the material suitable for preclinical and/or good laboratory practice toxicology studies and avoided formation key high-energy intermediates summarized.
During the process development of a pharmaceutical advanced intermediate, new chemistry using an aqueous workup resulted in discovery hydrated crystal form this intermediate. This showed thermal instability at relatively low temperature compared to original anhydrous form. Thermal stability and associated safety hazards were investigated order ensure transportation © 2017 American Institute Chemical Engineers Process Saf Prog 37: 263–267, 2018
The unnatural, alkyne-containing nucleoside analog islatravir (MK-8591) is synthetically accessed through a biocatalytic cascade starting from 2-ethynylglycerol as building block. Herein, we describe the development of an efficient synthesis this block including initial route, route scouting and final process development. Key challenges that have been overcome are safe acetylenic nucleophile addition to appropriate ketone, identification 2-ethynylpropane-1,2,3-triol derivative with favorable...
Asymmetric transfer hydrogenation (ATH) is a commonly used transformation in the pharmaceutical industry for reduction of ketones to establish key stereocenters. Yet, potential hydrogen gas generation during reaction, workup, and waste handling processes could be overlooked, resulting serious safety issues such as container overpressurization or fire. In this study, multiple module calorimeter (MMC) testing along with micro-GC tests small scale (1–2 mL) representative lab samples were...
Process Safety scientists in the pharmaceutical industry are tasked with keeping laboratories, manufacturing facilities, people, and environment safe from thermal runaway reactions. This group of highly trained chemists engineers has forged an alliance stretching across company lines to help ensure safety global sector. In this Commentary, we share our challenges, strategies, opportunities for working together respective companies external vendors. We discuss three platforms collaborating...
Process safety testing is critical for small molecule active pharmaceutical ingredient (API) scale-up and manufacturing by proactively identifying any process hazards, including environmental industrial hygiene issues. The intent of this contribution to describe how Merck & Co., Inc. Kenilworth, NJ (known as MSD outside the U.S. Canada) manages pilot plant scale operations with a stagewise approach. Several case studies will be discussed.
The unnatural, alkyne-containing nucleoside analog islatravir (MK-8591) is synthetically accessed through a biocatalytic cascade starting from 2-ethynylglycerol as building block. Herein, we describe the development of an efficient synthesis this block including initial route, route scouting and final process development. Key challenges that have been overcome are safe acetylenic nucleophile addition to appropriate ketone, identification 2-ethynylpropane-1,2,3-triol derivative with favorable...
A simple and efficient process to prepare Uprifosbuvir intermediate, 2′-deoxy-α-2′-chloro-β-2′-methyluridine (1), from bis-pivaloyl tertiary alcohol 5a is described. The key discoveries are a novel BSA-promoted anhydrouridine formation catalyzed by HCl as an additive milder safe Me2SiCl2-promoted chlorination of anhydrouridine. These collectively enabled the establishment robust toward compound 1, which was demonstrated successfully at plant scale.
Enol ethers derived from 2-bromomalonaldehyde are useful intermediates for the preparation of functionalized imidazolecarboxaldehydes. Recent work in our group required that bromomalonaldehyde be converted to an enol ether on a large scale and used campaign generate late-stage intermediate synthesis investigational active pharmaceutical ingredient (API). 2-Bromomalonaldehyde was into several each evaluated with respect its suitability long-term storage temperature at which thermal...