1146955-36-3

Upstream product

• 186407-74-9 4-bromoindazole 
• 885675-66-1 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]-pyrimidin-4-yl)morpholine 
• 1416327-31-5 2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-ylboronic acid 
• 22288-78-4 Methyl 3-aminothiophene-2-carboxylate 
• 16233-51-5 1H-thieno[3,2-d]pyrimidine-2,4-dione 
• 16234-14-3 2,4-dichlorothieno[3,2-d]pyrimidine 
• 16234-15-4 2-chloro-4-morpholinothieno[3,2-d]pyrimidine 
• 55289-36-6 3-bromo-2-methylaniline 
• 885618-31-5 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 
• 1416327-30-4 1-((4-(methylsulfonyl)piperazin-1-yl)methyl)-1H-benzotriazole 

Downstream Products

• 957054-50-1 4-(2-(1H-indazol-4-yl)-6-((4-(methylsulfonyl)-piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)-morpholine bis-methanesulfonate 

Relevant academic research and scientific papers

A practical synthesis of a PI3K inhibitor under noncryogenic conditions via functionalization of a lithium triarylmagnesiate intermediate

We report a practical synthesis of PI3K inhibitor GDC-0941. The synthesis was achieved using a convergent approach starting from a thienopyrimidine intermediate through a sequence of formylation and reductive amination followed by Suzuki-Miyaura cross-coupling. Metalation of the thienopyrimidine intermediate involving the intermediacy of triarylmagnesiates allowed formylation under noncryogenic conditions to produce the corresponding aldehyde. We also investigated aminoalkylation via a benzotriazolyl-piperazine substrate as an alternative to the reductive amination route. We evaluated both palladium and nickel catalyzed processes for the borylation and Suzuki-Miyaura cross-coupling. Final deprotection and salt formation afforded the API.