454248-65-8

Upstream product

• 697763-59-0 (R)-2-{[1-Phenyl-meth-(E)-ylidene]-amino}-propan-1-ol 
• 74609-49-7 (2R)-2-[(phenylmethyl)amino]-1-propanol 
• 458560-70-8 (R)-3-benzyl-4-methyl-1,2,3-oxathiazolidine-2-oxide 
• 100-52-7 benzaldehyde 

Downstream Products

• 458560-75-3 (R)-N-benzyl-2-amino-1-fluoropropane 
• 1417287-46-7 C₁₅H₁₆ClN₃S 

Relevant academic research and scientific papers

Structure-based drug design of novel potent and selective tetrahydropyrazolo[1,5-a]pyrazines as ATR inhibitors

A saturation strategy focused on improving the selectivity and physicochemical properties of ATR inhibitor HTS hit 1 led to a novel series of highly potent and selective tetrahydropyrazolo[1,5-a]pyrazines. Use of PI3Kα mutants as ATR crystal structure surrogates was instrumental in providing cocrystal structures to guide the medicinal chemistry designs. Detailed DMPK studies involving cyanide and GSH as trapping agents during microsomal incubations, in addition to deuterium-labeled compounds as mechanistic probes uncovered the molecular basis for the observed CYP3A4 TDI in the series. (Chemical Equation Presented).

Fluoroamines via chiral cyclic sulfamidates

N-benzyl [1,2,3]-oxathiazolidine 2,2-dioxides (cyclic sulfamidates) were synthesized from their corresponding β-amino alcohols and used as substrates in fluorination reactions with tetrabutylammonium fluoride (TBAF). After desulfonation of the intermediates, the N-benzyl fluoroamines were debenzylated by transfer hydrogenolysis with Pd/C to yield (S) and (R)-2-amino-1-fluoropropanes (2b and 3b, respectively, both with 95% ee). The reactions were carried out on multi-gram scale without the need for chromatographic purification of the intermediates. In the presence of carbonate, the (S)- and (R)-N-benzylfluoroamines underwent intramolecular cyclizations in which fluoride was displaced to yield cyclic carbamates 13 and 14.