51064-65-4Relevant articles and documents
Improved Synthesis of MediPhos Ligands and Their Use in the Pd-Catalyzed Enantioselective N-Allylation of Glycine Esters
Albat, Dominik,Neud?rfl, J?rg-Martin,Reiher, Martin,Schmalz, Hans-Günther
supporting information, p. 4237 - 4242 (2021/08/24)
A new class of chiral C2-symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd-catalyzed asymmetric N-allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional SN2-coupling of a tartrate-derived ditosylate with 6-alkyl-2-bromophenols followed by double lithiation/phosphanylation. This method gave access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd-catalyzed N-allylation of tert-butyl glycinate with racemic (E)-2,8-dimethylnona-5-en-4-yl methyl carbonate (up to 95 % ee). In addition, the analogous transformation of tert-butyl glycinate with methyl (E)-nona-5-en-4-yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline-derived dipeptide analogs ProM-17 and ProM-21.
Optimization of an electrolyte system for the simultaneous separation of nelfinavir mesylate and two impurities by micellar electrokinetic chromatography
Bastos, Carina A.,Gomes, Cláudia R. B.,De Souza, Marcus V. N.,De Oliveira, Marcone A. L.
, p. 887 - 898 (2015/05/20)
A methodology for the simultaneous determination of nelfinavir mesylate and the impurities 3-hydroxy-2-methylbenzoic acid and (2R,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl) octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-(phenylthio)butan-2-aminium benzoate by micellar electrokinetic chromatography, with an analysis time of 25 min, was proposed. An electrolyte composed of sodium tetraborate buffer (pH 9.24; 25 mmol L-1), sodium dodecyl sulphate (9 mmol L-1) and methanol (10percent, v/v) was optimized using a mixed-level factorial design, with direct detection at 200 nm. After evaluating some figures of merit, such as selectivity, linearity, precision, limit of detection, limit of quantification, accuracy and robustness (using Youden's test), the method was successfully applied to the analysis of nelfinavir mesylate and its impurities in a pharmaceutical formulation. The optimized methodology is demonstrated to be useful in the determination of these analytes in a synthesis monitoring process, in raw materials and in pharmaceutical formulations, while offering low solvent consumption, requiring a small sample and using non-specific columns as advantages.
A synthesis of the HIV-protease inhibitor nelfinavir from D-tartaric acid
Albizati, Kim F.,Babu, Srinivasan,Birchler, Angela,Busse, Juliette K.,Fugett, Michelle,Grubbs, Alan,Haddach, Aubrey,Pagan, Miguel,Potts, Barbara,Remarchuk, Travis,Rieger, Dale,Rodriguez, Rick,Shanley, Jim,Szendroi, Robert,Tibbetts, Tony,Whitten, Kathleen,Borer, Bennett C.
, p. 6481 - 6485 (2007/10/03)
This letter describes a new synthesis of the HIV-protease inhibitor nelfinavir. The synthesis features a selective opening of a D-tartaric acid-derived cyclic sulfate with nitrogen nucleophiles.
