1001180-45-5Relevant articles and documents
Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib
Han, Chong,Savage, Scott,Al-Sayah, Mohammad,Yajima, Herbert,Remarchuk, Travis,Reents, Reinhard,Wirz, Beat,Iding, Hans,Bachmann, Stephan,Fantasia, Serena M.,Scalone, Michelangelo,Hell, André,Hidber, Pirmin,Gosselin, Francis
, p. 4806 - 4809 (2017/09/23)
A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2 starting material was prepared via a nitrilase biocatalytic resolution, halogen-metal exchange/anionic cyclization, and a highly dia
PROCESS OF MAKING HYDROXYLATED CYCLOPENTAPYRIMIDINE COMPOUNDS AND SALTS THEREOF
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Paragraph 0070-0071, (2015/04/15)
The invention provides new processes for making and purifying salts of hydroxylated cyclopentapyrimidine compounds, which are useful as AKT inhibitors used in the treatment of diseases such as cancer, including the monohydrochloride salt of (S)-2-(4-chlor
Synthesis of Akt inhibitor ipatasertib. part 1. Route scouting and early process development of a challenging cyclopentylpyrimidine intermediate
Lane, Jonathan W.,Spencer, Keith L.,Shakya, Sagar R.,Kallan, Nicholas C.,Stengel, Peter J.,Remarchuk, Travis
supporting information, p. 1641 - 1651 (2015/02/02)
Herein, the route scouting and early process development of a key cyclopentylpyrimidine ketone intermediate toward the synthesis of Akt inhibitor Ipatasertib are described. Initial supplies of the intermediate were prepared through a method that commenced with the natural product (R)-(+)-pulegone and relied on the early construction of a methyl-substituted cyclopentyl ring system. The first process chemistry route, detailed herein, enabled the synthesis of the ketone on a hundred-gram scale, but it was not feasible for the requisite production of multikilogram quantities of this compound and necessitated the exploration of alternative strategies. Several new synthetic approaches were investigated towards the preparation of the cyclopentylpyrimidine ketone, in either racemic or chiral form, which resulted in the discovery of a more practical route that hinged on the initial preparation of a highly substituted dihydroxypyrimidine compound. The cyclopentane ring in the target was then constructed through a key carbonylative esterification and subsequent tandem Dieckmann cyclization-decarboxylation sequence that was demonstrated in a racemic synthesis. This proof-of-concept was later developed into an asymmetric synthesis of the cyclopentylpyrimidine ketone, which will be described in a subsequent paper, along with the synthesis of Ipatasertib.
