반응 #543271

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1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-ethanone

4,6-difluoro-1-methyl-1H-indazole

n-BuLi

→

title compound

수율 41.0%

1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethanol

수율 41.0%

용매

THF

THF

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후처리

1. 1
   workup.STIRRINGThe resulting solution was stirred at this temperature for 3 hours
2. 2
   workup.STIRRINGstirred overnight
3. 3
   기타The reaction mixture was quenched with water
4. 4
   추출extracted with EtOAc for three times
5. 5
   세척washed with brine
6. 6
   건조dried over Na2SO4
7. 7
   기타The crude product was purified with flash chromatography (CH2Cl2:MeOH 95:5)

실험 절차

To a solution of 4,6-difluoro-1-methyl-1H-indazole (600 mg, 3.57 mmol) in 20 mL of anhydrous THF at −78° C. was added n-BuLi (1.6M solution in hexane, 2.56 mL, 4.1 mmol). The solution was stirred at this temperature for 1 hour and then a solution of 1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-ethanone (698 mg, 3.57 mmol) in 10 mL of anhydrous THF was added at −78° C. dropwise. The resulting solution was stirred at this temperature for 3 hours and slowly warmed up to room temperature and stirred overnight. The reaction mixture was quenched with water, extracted with EtOAc for three times. The organic layers were combined and washed with brine, dried over Na2SO4. The crude product was purified with flash chromatography (CH2Cl2:MeOH 95:5) to give the title compound as a yellow oil (530 mg, 41%). 1H-NMR (400 MHz, CDCl3) δ ppm 8.05 (d, 1H), 8.0 (s, 1H), 7.85 (s, 1H), 7.1 (d, 1H), 6.85 (d, 1H), 4.0 (s, 3H), 2.3 (s, 3H). LCMS (method B): [MH]+=363.9, tR=2.15 min.

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