Water → 2-((2-Hydroxy-ethyl)-{4-[4-((r)-1-phenyl-ethylamino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-benzyl}-amino)-ethanol

HRID 1295654Notes

Reaction equation

HRID 1295654 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:26][C:12]3[N:13]=[CH:14][N:15]=[C:16]([NH:17][C@@H:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH3:19])[C:11]=3[CH:10]=2)=[CH:5][CH:4]=1.O.[CH2:28]1[O:30][CH2:29]1.C1C[O:34][CH2:33][CH2:32]1>>[OH:34][CH2:33][CH2:32][N:1]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:26][C:12]3[N:13]=[CH:14][N:15]=[C:16]([NH:17][C@@H:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH3:19])[C:11]=3[CH:10]=2)=[CH:5][CH:4]=1)[CH2:29][CH2:28][OH:30]

Participants

5

Reactant 4

HCID 962WaterHCID 6354Ethylene OxideHCID 8028TetrahydrofuranHCID 59756727[6-(4-Aminomethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenyl-ethyl)-amine

Product 1

HCID 691817912-((2-Hydroxy-ethyl)-{4-[4-((r)-1-phenyl-ethylamino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-benzyl}-amino)-ethanol

Conditions

Temperature
0 °C

Procedure

[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.

Workup

  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

Sources & evidence

ORD record
ord-36f4fffc7bde4c56b93615595457c71a
Source dataset
uspto-grants-2007_07
Patent number
US07244729B2

Reaction notes

Loading…