反应详情

温度

60 °C

In a 10 mL round-bottomed flask, (S)-2-(3-(2-chloro-4-fluorophenylsulfonyl)pyrrolidin-1-yl)pyrimidine-4-carbonitrile (example 73) (50 mg, 136 μmol, 1 eq) was combined with acetonitrile (4 mL) to give a light yellow solution. 1-Methylpiperazine (20.7 mg, 22.9 μl, 204 μmol, 1.5 eq) and DIEA (35.2 mg, 47.6 μl, 273 μmol, 2 eq) were added. The reaction mixture was heated to 60° C. and stirred for 20 h. After that, 1-methylpiperazine (0.7 eq) and of DIEA (1 eq) were added. The reaction mixture was stirred at 60° C. for 5 h. After that, additional 1-methylpiperazine (1 eq) and DIEA (1.2 eq) were added. The reaction mixture was stirred at 60° C. for 16 h. The crude reaction mixture was concentrated in vacuo. The reaction mixture was poured into aqueous 5% Na2CO3 solution and extracted with EtOAc (3×10 mL). The organic layers were combined and washed with saturated aqueous NaCl solution (1×). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10 g, CH2Cl2/MeOH 98/2) to yield a light yellow foam (42 mg, 69%). MS: m/z=447.1409 [M+H]+.

1. customto give a light yellow solution
2. stirringThe reaction mixture was stirred at 60° C. for 5 h
3. stirringThe reaction mixture was stirred at 60° C. for 16 h
4. customThe crude reaction mixture
5. concentrationwas concentrated in vacuo
6. additionThe reaction mixture was poured into aqueous 5% Na2CO3 solution
7. extractionextracted with EtOAc (3×10 mL)
8. washwashed with saturated aqueous NaCl solution (1×)
9. dry with materialThe organic layers were dried over Na2SO4
10. concentrationconcentrated in vacuo
11. customThe crude material was purified by flash chromatography (silica gel, 10 g, CH2Cl2/MeOH 98/2)