反应详情

温度

0 °C

[6-(4-Aminomethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenyl-ethyl)-amine (step 40.5, 0.5 g, 1.46 mmol) is dissolved in THF (7.5 ml) and water (0.75 ml) and cooled to −10° C. A stream of ethylene oxide is then passed through the solution for about 40 min (amount of ethylene oxide absorbed 5 to 6 g). The flask is sealed and the mixture stirred at 0° C. for 30 min and then at 50° C. for 16 h. The clear yellow solution is cooled and the solvents evaporated. The residue is purified by flash chromatography on 34 g of silica gel. The column is eluted using a mixture of dichloromethane/methanol with gradually increasing concentrations of methanol starting with 100:1.25 and ending with 100:2.5 and then switching to dichloromethane/methanol/conc. ammonia starting with 100:2.5:0.125 and ending with 100:10:0.5. Fractions containing the title compound were pooled and concentrated on a rotary evaporator. The residue is taken up in a small amount of dichloromethane and the resulting solid collected by filtration; m.p. 194-197° C.; Rf (dichloromethane/methanol/conc. ammonia 90:10:1)=0.21; MS-ES+: (M+H)+=432.

1. custom(amount of ethylene oxide absorbed 5 to 6 g)
2. customThe flask is sealed
3. waitat 50° C. for 16 h
4. temperatureThe clear yellow solution is cooled
5. customthe solvents evaporated
6. customThe residue is purified by flash chromatography on 34 g of silica gel
7. washThe column is eluted
8. additiona mixture of dichloromethane/methanol
9. temperaturewith gradually increasing concentrations of methanol starting with 100:1.25
10. additionFractions containing the title compound
11. concentrationconcentrated on a rotary evaporator
12. filtrationthe resulting solid collected by filtration