Dimethylamine → N2-(4-{4-amino-1-[2-(dimethylamino)ethyl]-1H-pyrazolo [3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate (Intermediate 4) (0.080 g, 0.15 mmol), dimethylamine (2.0 M in THF, 0.07 mL, 0.15 mmol), triethylamine (0.021 mL, 0.15 mmol), and sodium iodide (0.021 g, 0.15 mmol) in DMF (2.5 mL) was heated in a resealable tube at 70° C. for 15 h. Additional dimethylamine solution (0.10 mL) was added and the reaction mixture was heated at 70° C. for 20 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. Water (5 mL) was added and the resulting precipitate was collected by filtration and purified by silica gel column chromatography (elution with 20% MeOH:CH2Cl2 to 10:30:60 Et3N:MeOH:CH2Cl2); the appropriate fractions were combined and concentrated to afford N2-(4-{4-amino-1-[2-(dimethylamino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide as a white solid (0.009 g, 0.02 mmol). RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile—0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 10.52. MS: M+485.2.

Provenance & Evidence