反应详情

A mixture of K2CO3 (1.0 g), 1-(2-chloroethyl)pyrrolidine hydrochloride (66 mg) and tert-butyl 5-amino-2-methylthio-4-(3-hydroxyphenyl)-quinazoline-6-carboxamide (example 26a, 121 mg) in acetone was heated overnight at reflux. The mixture was cooled to room temperature, the solids were removed by filtration and the filtrate concentrated under reduced pressure. The residue was taken up in EtOAc and washed with water and brine. The organic phase was dried (MgSO4) and concentrated in vacuo. The title compound was purified by HPLC using a Luna C-18 column with the following gradient: 10% aq. CH3CN/CH3CN/0.1% aq. TFA=72/25/3 to 27/70/3 (v/v/v) in 30 min. The title compound was lyophilized from a nixture of water, TFA is and CH3CN.

1. temperaturewas heated overnight
2. temperatureat reflux
3. customthe solids were removed by filtration
4. concentrationthe filtrate concentrated under reduced pressure
5. washwashed with water and brine
6. dry with materialThe organic phase was dried (MgSO4)
7. concentrationconcentrated in vacuo
8. customThe title compound was purified by HPLC