Patent ID: 8354528
Filing Date: 2013-01-15
Classification: A61P,C07D,C07F

Abstract:
1. A process for preparing 4-(2-(1H-indazol-4-yl)-6-(4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine of Formula I: and pharmaceutically acceptable salts thereof, comprising (a) reacting methyl 3-aminothiophene-2-carboxylate 1 and potassium cyanate to yield thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione 2 (b) reacting 2, phosphoryl trichloride, and N,N-dimethylaniline to yield 2,4-dichlorothieno[3,2-d]pyrimidine 3 (c) reacting 3 and morpholine to yield 4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine 4 (d) reacting 4 with n-butyllithium and then dimethylformamide to yield 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 5 (e) reacting 5 and 4-(methylsulfonyl)piperazin-1-ium chloride 8 to yield 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 9 (f) reacting 9,2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole 10, and a palladium catalyst to yield 4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine 14 (g) reacting 14 with an acid to yield Formula I.