2-Chlorobenzylamine → [3-[6-(2-chloro-benzylamino)-pyridin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine

Participants

Reaction Conditions

Reaction Steps

A sealed tube was charged with [3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine (from Example 32 supra) (350 mg, 0.655 mmol), 2-chlorobenzylamine (130 mg, 0.918 mmol), Pd2(dba)3 (38 mg, 0.066 mmol), DavePhos (52 mg, 0.132 mmol), t-BuONa (88 mg, 0.917 mmol) and dioxane (16 mL). The mixture was stirred at 102° C. under an atmosphere of N2 for 15 hours. After cooling to room temperature, the mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 20 g, 200-300 mesh, eluting with dichloromethane:MeOH, 80:1) to give [3-[6-(2-chloro-benzylamino)-pyridin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine. (Yield 276 mg, 71%).

Provenance & Evidence