反应详情

温度

70 °C

In a 25 mL round-bottom flask were placed 250 mg (0.84 mmol, 1.1 equiv) of 4-chloro-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidine-7-carboxylic acid ethyl ester and 131 mg (0.77 mmol, 1 equiv) m-bromoaniline in 10 mL of ethanol with one drop conc HCl. The flask was equipped with a reflux condenser and heated at 70° C. for 4 h. The mixture was allowed to cool to rt and ethanol was concentrated in vacuo. The resulting crude residue was re-dissolved in EtOAc (10 mL), poured into a separatory funnel and washed with satd NaHCO3 (1×10 mL). The organic layer was dried (MgSO4), filtered and concentrated to give a crude oil. The crude material was further purified by MPLC (Biotage) using 1/4 EtOAc/Hex to provide 257 mg (77%) of the desired product, 14, as a white powder. 1H-NMR (CDCl3-d) δ 8.44 (s, 1H), 7.92 (s, 1H), 7.55 (m, 1H), 7.23 (m, 2H), 7.08 (s, 1H), 4.22 (q, 2H), 3.14 (m, 4H), 2.91 (m, 1H), 2.39 (m, 1H), 2.14 (m, 1H), 1.30 (t, 3H); LCMS RT=3.48 min; [M+H]+=432.

1. customIn a 25 mL round-bottom flask were placed
2. customThe flask was equipped with a reflux condenser
3. temperatureto cool to rt
4. concentrationethanol was concentrated in vacuo
5. dissolutionThe resulting crude residue was re-dissolved in EtOAc (10 mL)
6. additionpoured into a separatory funnel
7. washwashed with satd NaHCO3 (1×10 mL)
8. dry with materialThe organic layer was dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a crude oil
12. customThe crude material was further purified by MPLC (Biotage)