反应详情

To a suspension of 7-bromo-5-chloro-1H-indazole (23.7 g, 102 mmol) in tetrahydrofuran (400 mL) at 0° C. was added sodium hydride (2.70 g, 113 mmol) in portions to control the release of hydrogen. The ice bath was removed and the reaction was stirred at room temperature for 20 min. The reaction was then cooled to −78° C. and treated with tert-butyllithium (1.7 M, 126 mL, 215 mmol) dropwise over 20 min. The reaction was allowed to gradually warm to −40° C. in the icebath over 1 h. The reaction was re-cooled to −78° C. and treated with an excess of freshly crushed pellets of dry ice. The ice bath was removed and the reaction allowed to gradually warm to room temperature. The reaction was diluted with diethyl ether, and washed with water until most of the insoluble solid was dissolved. The ethereal was washed once more with 1M sodium hydroxide, which was combined with the other aqueous layers. The ethereal was discarded. The combined aqueous washings were cooled to 0° C., and made acidic by the cautious addition of concentrated hydrochloric acid to give a precipitate. The resulting solid was collected by filtration to give the product as a light tan solid. The product was air dried overnight and then pumped under high vaccuum to remove any trace of water to give 15.9 g (79%) which was used without purification. 1H-NMR (d6-DMSO, 500 MHz) δ 13.29 (bs, 1H), 8.18 (s, 1H), 8.14 (d, J=1.8 Hz, 1H), 7.86 (d, J=2.1 Hz, 1H); 13C NMR (126 MHz, d6-DMSO) δ ppm 165.6, 136.5, 133.6, 128.0, 125.5, 124.8, 123.9, 115.5. Mass spec.: 196.97 (MH)+.

1. customThe ice bath was removed
2. temperatureThe reaction was then cooled to −78° C.
3. temperatureto gradually warm to −40° C. in the icebath over 1 h
4. temperatureThe reaction was re-cooled to −78° C.
5. customThe ice bath was removed
6. temperatureto gradually warm to room temperature
7. additionThe reaction was diluted with diethyl ether
8. washwashed with water until most of the insoluble solid
9. dissolutionwas dissolved
10. washThe ethereal was washed once more with 1M sodium hydroxide, which
11. temperatureThe combined aqueous washings were cooled to 0° C.
12. additionmade acidic by the cautious addition of concentrated hydrochloric acid
13. customto give a precipitate
14. filtrationThe resulting solid was collected by filtration