118994-89-1Relevant articles and documents
A general route to the Streptomyces-derived inthomycin family: The first synthesis of (+)-inthomycin B
Webb, Michael R.,Donald, Craig,Taylor, Richard J. K.
, p. 549 - 552 (2006)
A concise, convergent and stereocontrolled synthesis of (+)-inthomycin B, based on the Stille coupling of a stannyl-diene with an oxazole vinyl iodide unit, is described. The asymmetric centre was introduced using the Kiyooka ketene acetal/amino acid-derived oxazaborolidinone procedure.
Application of C-H Functionalization in the Development of a Concise and Convergent Route to the Phosphatidylinositol-3-kinase Delta Inhibitor Nemiralisib
Bream, Robert N.,Clark, Hugh,Edney, Dean,Harsanyi, Antal,Hayler, John,Ironmonger, Alan,Mc Cleary, Nadine,Phillips, Natalie,Priestley, Catherine,Roberts, Alastair,Rushworth, Philip,Szeto, Peter,Webb, Michael R.,Wheelhouse, Katherine
, p. 529 - 540 (2021/03/01)
This paper describes the development of an improved and scalable method for the manufacture of nemiralisib, a phosphatidylinositol-3-kinase delta inhibitor. Incorporation of three consecutive catalytic reactions, including a palladium-catalyzed C-H functionalization and an iridium-catalyzed borylation, significantly simplified and shortened the synthetic sequence. The revised route was successfully implemented in a pilot plant on a multikilogram scale to deliver >100 kg of product.
Development of Flexible and Scalable Routes to Two Phosphatidinylinositol-3-kinase Delta Inhibitors via a Common Intermediate Approach
Edney, Dean,Hulcoop, David G.,Leahy, John H.,Vernon, Lois E.,Wipperman, Mark D.,Bream, Robert N.,Webb, Michael R.
, p. 368 - 376 (2018/03/22)
This paper describes the discovery and development of a flexible route to two candidate drug molecules by a common intermediate approach. Key reactions include Negishi and Suzuki couplings to form biaryl bonds. Conditions for a Miyaura borylation of heteroaryl bromides were also developed. Heteroaryl trifluoroborates and aryl chlorides were used as coupling partners in the Suzuki reaction, thereby minimizing detrimental side reactions such as protodeboronation and oxidative homocoupling. A complementary set of reaction conditions using pinacolboronates with potassium bifluoride as an additive were also developed and used to make 5 kg of drug substance for use in early-phase clinical trials.
