反应详情

A solution of n-butyllithium (2.5 M in hexanes, 0.27 mL, 0.66 mmol) was added dropwise by syringe to a stirring solution of 4-((4-chloro-6-iodo-2-methoxyquinolin-3-yl)methyl)-N,N-dimethylaniline (300 mg, 0.663 mmol, Intermediate 24: step c) in dry THF (5 mL) at −78° C. After 2 minutes, a solution of (2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (143 mg, 0.663 mmol, Intermediate 19: step b) in dry THF (1 mL) was added dropwise by syringe. After 3 minutes, the flask was removed from the cooling bath and allowed to warm. After 5 minutes, the flask was placed into an ice-water bath. After 15 minutes, water (5 mL) and ethyl acetate (25 mL) were added. The biphasic mixture was partitioned between half-saturated aqueous sodium chloride solution (20 mL) and ethyl acetate (25 mL). The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (4 g) was added to the filtrate and the solvents were removed by rotary evaporation to provide a free-flowing powder. The powder was loaded onto a silica gel column. Elution with 30% ethyl acetate-hexanes initially, grading to 90% ethyl acetate-hexanes provided the title compound as an off-white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.03 (s, 1H), 7.83-7.78 (m, 1H), 7.34 (d, J=8.8 Hz, 1H), 7.23-7.17 (m, 2H), 7.00-6.90 (m, 3H), 6.68-6.61 (m, 2H), 4.19 (s, 2H), 4.11 (s, 3H), 3.92 (s, 3H), 3.45 (s, 1H), 2.88 (s, 6H), 2.55 (s, 3H), 2.39 (s, 3H); MS (ESI): mass calcd. for C30H31ClN6O2, 542.2. m/z found, 543.1 [M+H]+.

1. waitAfter 3 minutes
2. customthe flask was removed from the cooling bath
3. temperatureto warm
4. waitAfter 5 minutes
5. customthe flask was placed into an ice-water bath
6. waitAfter 15 minutes
7. additionwater (5 mL) and ethyl acetate (25 mL) were added
8. customThe biphasic mixture was partitioned between half-saturated aqueous sodium chloride solution (20 mL) and ethyl acetate (25 mL)
9. customThe layers were separated
10. dry with materialThe organic layer was dried with sodium sulfate
11. filtrationthe dried solution was filtered
12. additionSilica gel (4 g) was added to the filtrate
13. customthe solvents were removed by rotary evaporation
14. customto provide a free-flowing powder
15. washElution with 30% ethyl acetate-hexanes initially