反应详情

温度

-35 °C

To (5-bromo-6-fluoro-pyridin-2-yl)-(5-fluoro-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (143, 0.600 g, 1.50 mmol) in 10.0 mL of tetrahydrofuran at −25° C. under nitrogen, isopropylmagnesium chloride (0.730 mL, 2.0 M in tetrahydrofuran, 1.46 mmol) was added and the reaction allowed to come to 5° C. over 1 hour. The reaction was then cooled to −35° C., and CuCN-2LiCl (2.0 mL, 0.75 M in tetrahydrofuran, 1.5 mmol) was added. After 5 minutes, 5-chloro-3-chloromethyl-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (142, 0.300 g, 0.996 mmol) in 4.0 mL of tetrahydrofuran was added and the reaction allowed to come to room temperature over 1 hour. The reaction was poured into dilute ammonia solution and extracted with ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexane. Appropriate fractions were combined and the solvent removed under vacuum to provide the desired compound (144, 130 mg). MS (ESI) [M+H]+=586.2.

1. waitAfter 5 minutes
2. waitto come to room temperature over 1 hour
3. extractionextracted with ethyl acetate
4. customThe organic layer was separated
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationthe filtrate concentrated under vacuum
8. customThe resulting material was purified by silica gel column chromatography
9. washeluting with 20-100% ethyl acetate in hexane
10. customthe solvent removed under vacuum