Rubikschemistry

Borane Picoline and 5-Ethyl-2-MethylPyridine Borane Mediated Reductive Amination

Synthesis /

Picoline borane (PICB) was developed with the objective of enhancing the thermal stability of pyridine borane (PYB). The incorporation of the ortho methyl group not only imparts the desired stability to the reagents but also gives distinctive reactivity, particularly evident in the context of reductive amination. PICB demonstrates utility under neat conditions with liquid substrates; […]

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Quench-Crystallization Development for an Intermediate of the Synthesis of Sotorasib

Hot Targets /

Antisolvent/cooling and quench crystallization methodologies stand as predominant techniques in the crystallization domain, widely employed for the purification of starting materials, intermediates, and active pharmaceutical ingredients (APIs), as well as for identifying suitable polymorphs for drug products in the pharmaceutical industry. Quench crystallization, compared to antisolvent/cooling crystallization, exhibits the capability to generate crystals in the

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Crystallization Process Development of Serabelisib (TAK117)

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Bulk powder properties (BPPs) of small molecule pharmaceuticals are intricately regulated in the latter stages of API process development. These properties include critical factors such as solubility, density, flowability, and hygroscopicity, each influenced by a combination of particle characteristics, including particle size distribution (PSD), particle shape, moisture content, and chemical composition. The pursuit of optimal

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Tetrabutylammonium Cyanoborohydride as a Reducing Agent

Synthesis /

Sodium cyanoboronhydride (NaBH3(CN)) as a reducing agent for reductive amination has lower solubility in aprotic solvents, restricting its application when these solvents are required. To overcome this limitation, Hutchins introduced tetrabutylammonium cyanoborohydride (TBAC), a soluble compound not only in protic and polar solvents, but also in most aprotic solvents such as DCM, hexane, benzene, and

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Sodium Cyanoborohydride (NaBH3(CN)) Medidated Reduction

Synthesis /

Reductive amination, also termed reductive alkylation, is one of the most popular methods for forming C-N bonds. The pivotal Borch reaction, disclosed in 1971, laid the groundwork for borohydride-promoted reductive amination. This reaction leverage sodium cyanoborohydride (NaBH3(CN)) as a reducing reagent to condense a ketone/aldehyde with an amine/aniline, forming a C-N bond. The reduction potential

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Sodium Triaceoxyborohydride Mediated Reductive Amination

Synthesis /

Sodium triacetoxyborohydride (NaBH(OAc)3, STAB-H) serves as a popular reducing reagent for direct reductive amination (DRA), alongside sodium cyanoboronhydride (NaBH3(CN)). In comparison to NaBH3(CN), STAB-H offers several advantages. Firstly, STAB-H is a safer reagent because it does not release toxic cyanide ions. Secondly, STAB-H exhibits high reactivity in various aprotic solvents, including DCE, THF, and dioxane.

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Approved and Clinical-Stage ERK Inhibitors

Hot Targets /

Extracellular signal-regulated kinase 1/2 (ERK1/2) occupies a pivotal position as the distal effector in the intricate RAS-RAF-MEK-ERK signaling pathway. Remarkably, ERK1/2 exhibits a substantially lower frequency of mutational events in comparison to its upstream counterparts, namely RAS, RAF, and MEK. This inherent genetic stability confers distinct advantages upon ERK1/2 as a therapeutic target. Although ERK1/2

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Approved and Clinical-Stage MEK Inhibitors

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MEK1/2, the third component within the RAS-RAF-MEK-ERK cascade known as the “classical” MAPK oncology pathway, acts as the intermediary in transmitting signals from RAS and RAF to ERK, thereby modulating critical cellular processes such as survival and proliferation. Consequently, MEK1/2 has emerged as a promising target for cancer therapy. Currently, four MEK inhibitors have received

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Byproduct Profile of Vestipitant (GW597599) During Urea Formation

Synthesis /

Vestipitant (GW597599), a potent NK-1 antagonist, consists of an asymmetric urea moiety. The synthesis of this urea functional group presents challenges due to the complex nature of the reaction partners, coupling reagents, stoichiometry of reactants/reagents, temperature, and so on. Throughout the process development, a diverse array of byproducts was observed, necessitating careful optimization. To mitigate

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Approved and Clinical-Stage RAF Inhibitors

Hot Targets /

The RAF family kinase plays a crucial role as a pivotal component within the RAS/RAF/MEK/ERK signaling pathway, which is a fundamental cellular pathway involved in various physiological processes. Deregulation in RAF kinases, with a particular emphasis on BRAF, are frequently observed in malignant conditions including melanomas and papillary thyroid cancers. Consequently, the targeted inhibition of

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