Development and a Practical Synthesis of the JAK2 Inhibitor LY2784544 was written by Mitchell, David;Cole, Kevin P.;Pollock, Patrick M.;Coppert, David M.;Burkholder, Timothy P.;Clayton, Joshua R.. And the article was included in Organic Process Research & Development in 2012.Reference of 141459-53-2 This article mentions the following:
The route selection and process research and development of a practical synthesis for JAK2 inhibitor LY2784544 is described. The first-generation synthesis route, similar to that used in discovery for derivatization of a benzylic amine moiety, was 14 overall steps and possessed several steps that required extensive development for large-scale production Route selection considerations led to a modified synthesis that utilized a novel vanadium-catalyzed carbon-carbon bond-forming arylation reaction for incorporation of the key benzylic morpholine moiety. A protecting group used to mask an amino pyrazole unit was modified from PMB to tert-Bu, resulting in a dramatic reduction in the overall length of the route. These two major changes resulted in an eight-step synthesis, which was six steps shorter than the first-generation synthesis. In the pilot plant, the new synthesis was scaled to produce >100 kg of LY2784544 in high yield and purity under GMP conditions. The overall development including the vanadium-catalyzed C-C bond-forming methodol., a ketone reductive deoxygenation, and a palladium-catalyzed amination is described. In the experiment, the researchers used many compounds, for example, 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2Reference of 141459-53-2).
1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Reference of 141459-53-2
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics