反应详情

温度

-25 °C

1.30 g (2.85 mmol) of 5-bromo-4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine and 750 mg (17.69 mmol) of anhydrous vacuum dried lithium chloride were dissolved under nitrogen in 50 mL of anhydrous THF. The resulting solution was cooled to −25° C. and 2.0 mL (4 mmol) of a 2 M solution of iso-propyl-magnesium chloride in anhydrous THF was added dropwise. The resulting mixture was allowed to stir at −25 to −5° C. for 2 h. 2.0 mL (7.4 mmol) of tri-n-butyltin chloride was added slowly to the resulting mixture. Upon complete addition the reaction mixture was allowed to stir for 18 h, allowing to warm to ambient temperature. The resulting reaction mixture was distributed between diethyl ether and a saturated aqueous solution of ammonium chloride. The aqueous phase was separated and extracted twice with diethyl ether. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes to afford 2.298 g (3.45 mmol, 121%) of 4-chloro-3-(4-fluoro-phenyl)-5-tributylstannanyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine as a colorless oil. 1H-NMR [500 MHz, d6-DMSO] δ: 8.13 (s, 1H), 7.77 (s, 1H), 7.49-7.45 (m, 2H), 7.27-7.22 (m, 2H), 5.66 (s, 2H), 3.55 (t, 2H), 1.63-1.47* (m, 6H), 1.34-1.08* (m, 12H), 0.89-0.80* (t, 9H), −0.12 (s, 9H) [*: compound contaminated with other tri-n-butyl tin side product(s) in shift ranges indicated, appearing as distinct sets of peaks with equal integration to desired product]; MS [MH+] m/z: 665+667.

1. additionUpon complete addition the reaction mixture
2. stirringto stir for 18 h
3. temperatureto warm to ambient temperature
4. customThe resulting reaction mixture
5. customThe aqueous phase was separated
6. extractionextracted twice with diethyl ether
7. dry with materialThe combined organic phases were dried over sodium sulfate
8. customevaporated
9. customThe residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes