反应详情

To a solution of 4-chloroquinazoline (2.0 g, 12.2 mmol) (Tobe, Masanori, et al., Bioorg. Med. Chem. 2003, 11(3), 383) and DIEA (3.2 mL, 18.2 mmol) in 40 mL IPA was added Boc-piperazine (1.96 g, 12.81 mmol). The reaction mixture was heated to reflux and stirred for 20 hours, after which it was cooled to room temperature and concentrated by rotary evaporation. The residue was dissolved in dichloromethane (DCM) and washed with 1N NaOH. The organic layer was dried (Na2SO4), filtered, and concentrated by rotary evaporation. The resulting oil was dissolved in 25 mL dioxane, and 4M HCl/dioxane (46 mL, 182 mmol) was added dropwise. The suspension was sonicated for 2 minutes and stirred 13 hours at room temperature, after which the reaction mixture was concentrated to dryness by rotary evaporation. The resulting amine HCl salt was dissolved in 2N NaOH and extracted with DCM. The organic layer was dried (Na2SO4), filtered, and concentrated by rotary evaporation. The resulting oil was purified on silica (9:1:0.02 DCM/MeOH/NR4OH) to give 4-piperazinylquinazoline as a yellow oil (2.5 g, 96%). 1H NMR (CDCl3, 400 MHz) δ 8.74 (s, 1H), 7.92-7.86 (m, 2H), 7.76-7.70 (m, 1H), 7.48-7.42 (m, 1H), 3.75 (t, J=4.9 Hz, 4H), 3.09 (t, J=4.9 Hz, 4H), 1.89 (br s, 1H). Rt 0.70. MS (ESI+) [M+H]+ 215.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux
3. concentrationconcentrated by rotary evaporation
4. dissolutionThe residue was dissolved in dichloromethane (DCM)
5. washwashed with 1N NaOH
6. dry with materialThe organic layer was dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated by rotary evaporation
9. dissolutionThe resulting oil was dissolved in 25 mL dioxane
10. customThe suspension was sonicated for 2 minutes
11. stirringstirred 13 hours at room temperature
12. concentrationafter which the reaction mixture was concentrated to dryness by rotary evaporation
13. dissolutionThe resulting amine HCl salt was dissolved in 2N NaOH
14. extractionextracted with DCM
15. dry with materialThe organic layer was dried (Na2SO4)
16. filtrationfiltered
17. concentrationconcentrated by rotary evaporation
18. customThe resulting oil was purified on silica (9:1:0.02 DCM/MeOH/NR4OH)