Water → HCID 136068468, compound

Participants

Reaction Steps

(S)-tert-Butyl 3-(2-(5-bromo-2-hydroxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylate (0.051 g, 0.105 mmol, prepared in a method analogous to that described in Synthesis 2-A), 4-fluorobenzene boronic acid (0.016 g, 0.114 mmol), palladium tetrakistriphenyl phosphine (0.028 g, 0.024 mmol) and potassium phosphate (0.051 g, 0.243 mmol) were dissolved in dimethyl acetamide (0.7 mL) and water (0.3 mL) and the mixture was heated in a microwave for 10 mins at 150° C. The mixture was filtered through a short plug of silica using ethyl acetate as eluent and the filtrate concentrated in vacuo. The residue was dissolved in methanol (1.2 mL) and 4M HCl in dioxane (1.2 mL) was added and the mixture stirred for 16 h. The mixture was concentrated and purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. The basic fractions were combined and purified by silica column chromatography, eluting with dichloromethane then 10% methanol in dichloromethane, to give the title compound as a yellow solid (0.013 g, 27%).

Provenance & Evidence