30698-33-0Relevant academic research and scientific papers
PROCESSES FOR THE PREPARATION OF NIRAPARIB AND INTERMEDIATES THEREOF
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Paragraph 000190, (2019/03/05)
The present invention relates to novel procedures and novel intermediates useful in the synthesis of Niraparib or any salt thereof.
Thiazole formation through a modified Gewald reaction
Mallia, Carl J.,Englert, Lukas,Walter, Gary C.,Baxendale, Ian R.
supporting information, p. 875 - 883 (2015/08/24)
The synthesis of thiazoles and thiophenes starting from nitriles, via a modified Gewald reaction has been studied for a number of different substrates. 1,4-Dithiane-2,5-diol was used as the aldehyde precursor to give either 2-substituted thiazoles or 2-substituted aminothiophenes depending on the substitution of the α-carbon to the cyano group.
Production of (R)-aminoglutethimide: A new route from 1 -chloro-4-nitrobenzene
Bunegar, Michael J.,Dyer, Ulrich C.,Evans, Graham R.,Hewitt, Richard P.,Jones, Stephen W.,Henderson, Neil,Richards, Christopher J.,Sivaprasad, Sivadasan,Skead, Benjamin M.,Stark, Mark A.,Teale, Eric
, p. 442 - 450 (2013/09/08)
The development of a short, safe and enantioselective route for the preparation of (R)-aminoglutethimide is described. The process was designed for economic large-scale manufacture of the bulk drug substance to acceptable quality standards, to allow clinical evaluation of the single enantiomer over the existing racemate. (R)-Aminoglutethimide was prepared from 1-chloro-4-nitrobenzene using a six-stage synthetic sequence, via chemoresolution of key intermediate racemic 4-cyano-4-(4-nitrophenyl)hexanoic acid using (-)-cinchonidine. The process allowed for preparation of several kilograms of the precursor (R)-nitroglutethimide, to cGMP at pilot-plant scale, along with demonstration of the final hydrogenation step to (R)-aminoglutethimide in the laboratory. This route avoids the problems of hazardous nitration technology, and therefore regio-isomer contamination of the product, associated with other procedures. The resolution chemistry described represents an improvement on literature procedures. Optimisation of the asymmetric Michael addition offers an attractive alternative approach.
