反应详情

温度

90 °C

To a suspension of 3-(3-bromo-5-chlorophenoxy)-4-methyl-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)pyridin-2(1H)-one (11-6; 100 mg, 0.224 mmol) and zinc cyanide (29 mg, 0.247 mmol) in DMF (1 mL) was added palladium tetrakis triphenylphosphine (51.9 mg, 0.045 mmol) and the mixture was degassed and heated to 90° C. for 20 minutes. After this time, additional zinc cyanide (29 mg, 0.247 mmol) and palladium tetrakis triphenylphosphine (51.9 mg, 0.045 mmol) were added and the mixture heated to 90° C. for 20 hours. The reaction mixture was then filtered through Gelman Acrodisc and purified on Gilson LC using a Luna column (10μ, C18, 250×21.2 cm) eluting with 5-95% ACN/water with 0.1% TFA). Fractions containing desired compound were combine and the solvent concentrated in vacuo on a rotary evaporator. The residue was further purified using RediSep (4 g) and eluting with a 0-65% EtOAc/CH2Cl2 gradient. The desired fractions were combined and the solvent removed on the rotary evaporator to provide the title compound. 1H NMR (CDCl3): δ 11.48 (br s, 1H), 8.55 (d, 1H), 8.26 (d, 1H), 7.40 (d, 1H), 7.27 (dd, 1H), 7.14 (dd, 1H), 7.09 (dd, 1H), 6.96 (dd, 1H), 6.09 (dd, 1H), 5.48 (s, 2H) and 2.08 (s, 3H) ppm. LRMS (M+1)=392.

1. customthe mixture was degassed
2. temperaturethe mixture heated to 90° C. for 20 hours
3. filtrationThe reaction mixture was then filtered through Gelman Acrodisc
4. custompurified on Gilson LC
5. washeluting with 5-95% ACN/water with 0.1% TFA)
6. additionFractions containing desired compound
7. concentrationthe solvent concentrated in vacuo on a rotary evaporator
8. customThe residue was further purified
9. washeluting with a 0-65% EtOAc/CH2Cl2 gradient
10. customthe solvent removed on the rotary evaporator