1001178-90-0Relevant articles and documents
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
, p. 1641 - 1651 (2014)
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.
COMBINATIONS OF AKT AND MEK INHIBITOR COMPOUNDS, AND METHODS OF USE
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Page/Page column 36-37, (2012/10/18)
The invention provides combinations comprising a) compound of formula I : (formula I), or a pharmaceutically acceptable salt thereof; and another agent selected from GDC-0973, PD-0325901, or a pharmaceutically acceptable salt thereof. The combinations are
PYRIMIDYL CYCLOPENTANES AS AKT PROTEIN KINASE INHIBITORS
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Page/Page column 52, (2009/03/07)
The present invention provides compounds of Formula (I), including tautomers, resolved enantiomers, diastereomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.
