反应详情

9.25 g of 1-(4-methoxybenzyl)-1H-indazole-3-carbonitrile (1-1-1, 35.1 mmol, 1 eq.) were suspended in 128 ml of dry methanol under a nitrogen atmosphere. 0.949 g (17.6 mmol, 0.5 eq.) of sodium methanolate were added. The reaction mixture was stirred for 18 hours at room temperature. To the resulting mixture were added 2.82 g (52.7 mmol, 1.5 eq.) of ammonium chloride and 1.0 ml (17.6 mmol, 0.5 eq.) of 100% acetic acid and stirred for 5 hours at 50° C. After cooling down at room temperature the mixture was concentrated in vacuo. The residue was partitioned between aq. half saturated sodium hydrogen carbonate solution and dichloromethane/isopropanol 4:1. The aqueous layer was extracted three times with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography to yield 6.45 g (23 mmol, 65.5%) of the analytically pure target compound.

1. stirringstirred for 5 hours at 50° C
2. temperatureAfter cooling down at room temperature the mixture
3. concentrationwas concentrated in vacuo
4. customThe residue was partitioned between aq. half saturated sodium hydrogen carbonate solution and dichloromethane/isopropanol 4:1
5. extractionThe aqueous layer was extracted three times with dichloromethane/isopropanol 4:1
6. washThe combined organic layers were washed with brine
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash chromatography
10. customto yield 6.45 g (23 mmol, 65.5%) of the analytically pure target compound