反应详情

温度

150 °C

Sodium azide (178 mg, 2.73 mmol) and triethylamine hydrochloride (356 mg, 2.59 mmol) were added to 2-chloro-N-[1-(cyanomethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide (Example 27; 300 mg, 0.78 mmol) in 1-methyl-2-pyrrolidinone (7 mL) and then heated at 150° C. for 3 hours. On cooling the mixture was diluted with EtOAc (100 mL) and washed with H2O (50 mL). The aqueous layer was acidified with citric acid and extracted with MeOH:DCM (1:19) and the combined organics dried (MgSO4), filtered and evaporated. The residue was purified by applying the material to a 10 g Isolute NH2 column in MeOH:DCM (1:9) (10 mL) and eluting with MeOH:DCM (1:9) (6×10 mL). The column was eluted with MeOH: 2M HCl in Et2O:DCM (5:4:45) (6×10 mL) and the relevant fractions evaporated to afford the title product (246 mg, 74%) as pale pink powder.

1. temperatureOn cooling the mixture
2. washwashed with H2O (50 mL)
3. extractionextracted with MeOH:DCM (1:19)
4. dry with materialthe combined organics dried (MgSO4)
5. filtrationfiltered
6. customevaporated
7. customThe residue was purified
8. washeluting with MeOH:DCM (1:9) (6×10 mL)
9. washThe column was eluted with MeOH
10. custom2M HCl in Et2O:DCM (5:4:45) (6×10 mL) and the relevant fractions evaporated