反应详情

4-Methyl-1H-pyrazolo[3,4-b]pyridine-3,6-diol (1 g, 6.05 mmol), 4-trifluoromethyl-piperidine-1-carbonyl chloride (1.436 g, 6.6 mmol) and triethylamine (1.68 ml, 12.11 mmol) were stirred in 25 ml of pyridine at room temp for 1 h. Addition of 0.5 ml of triethylamine was followed by stirring for 2 h, concentration and addition of ethyl acetate and water. The resulting precipitate was filtered off with suction and dried. Yield: 765 mg (37%) of 4-trifluoromethylpiperidine-1-carboxylic acid 6-hydroxy-4-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl ester. The organic phase was separated off, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 96 mg (5%) of 4-trifluoromethylpiperidine-1-carboxylic acid 6-hydroxy-4-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl ester. M+H+: 345.13; 102 mg (3%) of 4-trifluoromethylpiperidine-1-carboxylic acid 4-methyl-3-(4-trifluoromethylpiperidine-1-carbonyloxy)-1H-pyrazolo[3,4-b]pyridin-6-yl ester, M+H+: 524.20; 106 mg (3%) of 4-trifluoromethylpiperidine-1-carboxylic acid 6-hydroxy-4-methyl-1-(4-trifluoromethylpiperidine-1-carbonyl)-1H-pyrazolo[3,4-b]pyridin-3-yl ester, M+H+: 524.52; 54 mg (1.3%) of 4-trifluoromethylpiperidine-1-carboxylic acid 4-methyl-3-(4-trifluoromethylpiperidine-1-carbonyloxy)-1-(4-trifluoromethylpiperidine-1-carbonyl)-1H-pyrazolo[3,4-b]pyridin-6-yl ester, M+H+: 703.36.

1. concentrationconcentration and addition of ethyl acetate and water
2. filtrationThe resulting precipitate was filtered off with suction
3. customdried
4. customThe organic phase was separated off
5. concentrationconcentrated
6. custompurified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA)