Process and intermediates for the synthesis of (3-alkyl-5-piperidin-1-yl-3,3a-dihydro-pyrazolo[1,5-a]pyrimidin-7-yl)-amino derivatives and intermediates

US8076479B2 · kind B2 · utility

Assignee

• SCHERING CORPORATION · US

Inventors

• Frank Xing Chen · Plainsboro, US
• Kartik M. Keertikar · Plainsboro, US
• Shen-Chun Kuo · Union, US
• Hong-Chang Lee · Livingston, US
• Ramani Raghavan · Elmont, US
• George G. Wu · Berkeley Heights, US
• Ji Xie · Edison, US

Key dates

• Filing date: Aug 17, 2007
• Grant date: Dec 13, 2011
• Expiry date: May 30, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D487/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Disclosed is a process for the synthesis of compounds of Formula Iby sequentially aminating, first with a primary amine and then with a secondary amine, an intermediate compound of the structure of Formula E1,wherein R1 is a linear, branched, or cyclic alkyloxy functional group of the structure (—R2a—OH), R2a is a linear, branched or cyclic alkyl group, R2 is a linear, branched or cyclic alkyl group, and R3 is an alkylene-heterocycle, said process comprising forming intermediate compound of Formula E1 by reacting, in a refluxing reaction solvent selected from alcohols having 5 or less carbon atoms and mixtures of two or more thereof, a methanol solution of a salt of a 4-alkyl-3-amino-pyrazole compound of Formula C1,with a diamidization reagent selected from dimethylmalonate, monomethylmalonyl-chloride, and malonyl dichloride in the presence of a Lewis base having sufficient proton affinity to abstract a proton from the 1-position nitrogen on the pyrazole ring.