131065-11-7

Upstream product

• 14618-80-5 (R)-benzyl glycidol 
• 56552-80-8 (R)-3-benzyloxy-1,2-propanediol 
• 100-39-0 benzyl bromide 

Downstream Products

• 1220530-43-7 C₂₀H₂₀F₃N₃O₄ 
• 1220530-40-4 1-(((R)-2-allyloxy-3-azidopropoxy)methyl)benzene 
• 869071-14-7 (S)-2-Benzyloxymethyl-aziridine 
• 134964-79-7 (S)-1-((S)-2-Benzyloxymethyl-aziridin-1-yl)-2-methyl-3-phenyl-propan-1-one 
• 134964-71-9 (R)-1-((S)-2-Benzyloxymethyl-aziridin-1-yl)-2-methyl-3-phenyl-propan-1-one 
• 167259-23-6 1-((S)-2-Benzyloxymethyl-aziridin-1-yl)-propan-1-one 

Relevant academic research and scientific papers

Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties

Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

Intramolecular reductive amination strategy to the synthesis of (R)-N-Boc-2-hydroxymethylmorpholine, N-(3,4-dichlorobenzyl)(R)-2-hydroxymethylmorpholine, and (R)-2-benzylmorpholine

A concise high yielding enantioselective synthesis of (R)-N-Boc-2-hydroxymethylmorpholine, N-(3,4-dichlorobenzyl)(R)-2-hydroxymethylmorpholine, and (R)-benzylmorpholine has been achieved by employing proline-catalyzed asymmetric α-aminooxylation of aldehyde and palladium-catalyzed intramolecular reductive amination of azido aldehyde as the key steps.

Regioselective and Stereospecific Azidation of 1,2- and 1,3-Diols by Azidotrimethylsilane via a Mitsunobu Reaction

A one-pot regio- and stereospecific azidation reaction of 1,2- and 1,3-diols with azidotrimethylsilane (MB3SiN3) via a Mitsunobu reaction has been achieved. With 1,2- and 1,3-diols, the reaction of triphenylphosphine, diisopropyl azodicarboxylate, and Me3SiN3 in dichloromethane gave regioselective azidation at C-2 and C-3, respectively, in good yield (74-90% combined yield of 1a + 1b or of 2a + 2b). However, application of the same reaction conditions to a 1,4-diol led to the exclusive formation of the cyclic ether. The regioselectivity of this one-pot reaction is influenced by the solvent, the degree of steric bulk at C-2 of the 1,2-diol or at C-3 of the 1,3-diol, and the presence of electron-donating and electron-withdrawing groups near the secondary carbinol carbon. This selectivity is discussed in terms of the mechanistic model proposed by Mathieu-Pelta and Evans (Mathieu-Pelta, I.; Evans, S. A., Jr. J. Org. Chem. 1992, 57, 3409-3413), which involves reaction of the dioxaphospholane intermediate with Me3SiN3 to form oxyphosphonium ions 4 and 5.

On the use of C2-symmetric aziridines as chiral auxiliaries

A systematic study has been made of the utility of readily available C2-symmetric aziridines as auxiliaries for asymmetric alkylation and aldol reactions of amide enolates. Aziridines with suitably placed oxygen atoms in the side chains proved to be useful for alkylation reactions (d.e. values up to >98%) and the results are explained in terms of an intramolecularly chelated Z-enolate species, which could be observed directly by means of NMR spectroscopy. In contrast, aziridine auxiliaries lacking side-chain oxygens performed better in aldol reactions (syn selectivity up to 98% d.e.) for which a Zimmerman-Traxler transition state is proposed. After reaction, the axuiliaries can be cleaved off non-destructively under mild conditions to afford either optically pure aldehydes or carboxylic acids.