Patent ID: 8076479
Filing Date: 2011-12-13
Classification: C07D

Abstract:
1. A process for the synthesis of CDK inhibitor compounds having the structure of Formula I from an intermediate compound of the structure of Formula E1, wherein R 1 is a linear, branched, or cyclic alkyloxy functional group of the structure (—R 2a —OH), R 2a is a linear, branched or cyclic alkyl group, R 2 is a linear, branched or cyclic alkyl group, and R 3 is an alkylene-heterocycle, said process comprising: (a) forming intermediate compound of Formula E1 by reacting, in a refluxing reaction solvent selected from the group consisting of 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 the group consisting of dimethylmalonate, monomethylmalonylchloride, 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; (b) derivatizing the intermediate E1 prepared in Step (a) to provide the compound of Formula F1, wherein “X” is selected from the group consisting of chloride, bromide, iodide, fluoride, and a sulfonyl group; and (c) sequentially aminating the compound of Formula F1 with a primary amine, and then with a secondary amine, to form the compound of Formula 1.