反应详情

6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (95.0 mg, 0.213 mmol) was dissolved in THF (2.5 mL) and the flask was cooled in an ice water bath. Then, tert-butylmagnesium chloride (1.0 M solution in tetrahydrofuran, 0.60 mL, 0.60 mmol) was added via syringe, turning the reaction red. The reaction was stirred under nitrogen while being warmed to room temperature, and after 70 min the reaction was treated with MeOH (1.0 mL) and 5 N HCl (0.50 mL). The flask was fitted with a reflux condenser and put in a preheated oil bath (about 50° C.), and stirring was continued for 1 h. Then, the reaction was cooled to room temperature, diluted with MeOH, concentrated, and purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min using a total flow rate of 100 mL/min) to give 1-(6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)-2,2-dimethylpropan-1-ol (45.9 mg, 97.4% purity, 52% yield). 1H NMR (d6-DMSO, 400 MHz) δ 12.62 (br s, 1H), 9.61 (s, 1H), 8.63 (s, 1H), 8.53 (d, J=2.74 Hz, 1H), 8.21-8.14 (m, 2H), 6.88 (d, J=9.0 Hz, 1H), 4.31 (s, 1H), 3.86 (s, 3H), 2.85 (s, 3H), 0.91 (s, 9H). m/z (ESI, pos. ion) 420 (M+H)+.

1. temperaturethe flask was cooled in an ice water bath
2. customThe flask was fitted with a reflux condenser
3. customput in a preheated oil bath
4. stirring(about 50° C.), and stirring
5. temperatureThen, the reaction was cooled to room temperature
6. concentrationconcentrated
7. custompurified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min