Potassium Carbonate → 3-iodo-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 897890Notes

Reaction equation

HRID 897890 reaction equation
Cl.Cl.[I:3][C:4]1[C:12]2[C:7](=[N:8][CH:9]=[N:10][C:11]=2[NH2:13])[N:6]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[N:5]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:26][O:27][CH2:28][CH2:29]Br>CN(C)C=O.[I-].[K+]>[I:3][C:4]1[C:12]2[C:7](=[N:8][CH:9]=[N:10][C:11]=2[NH2:13])[N:6]([CH:14]2[CH2:19][CH2:18][N:17]([CH2:29][CH2:28][O:27][CH3:26])[CH2:16][CH2:15]2)[N:5]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl ether3×HCID 223473623-iodo-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride

Product 1

HCID 223469673-iodo-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 52.1%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-iodo-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (0.4 g, 0.00096 mol) and potassium carbonate (0.40 g, 0.0029 mol) in N,N-dimethylformamide (25 mL) was added 2-bromoethyl methyl ether (0.09 mL, 0.00096 mol) at room temperature. The heterogeneous mixture was stirred at 60° C. under an atmosphere of nitrogen for 7 hours. The reaction mixture was cooled to room temperature, and 2-bromoethyl methyl ether (0.045 mL, 0.00048 mol) was added. The mixture was stirred at 60° C. under an atmosphere of nitrogen for 16 hours. To the mixture to the room temperature, 2-bromoethyl methyl ether (0.019 mL, 0.00019 mol) and potassium iodide (0.008 g, 0.000048 mol) were added in order to complete the reaction. The mixture was stirred at 70° C. under an atmosphere of nitrogen for 7 hours. The solvent was removed under the reduced pressure. The residue was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane (4×50 mL). The combined organic extracts were washed with water, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure. The residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-50% over 30 min with 0.1 M ammonium acetate, 21 mL/min) to yield 3-iodo-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.2 g, 0.0005 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-95% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 6.4 min. MS: MH+ 403

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringThe mixture was stirred at 60° C. under an atmosphere of nitrogen for 16 hours
  3. customthe reaction
  4. stirringThe mixture was stirred at 70° C. under an atmosphere of nitrogen for 7 hours
  5. customThe solvent was removed under the reduced pressure
  6. customThe residue was partitioned between water and dichloromethane
  7. extractionThe aqueous layer was extracted with dichloromethane (4×50 mL)
  8. washThe combined organic extracts were washed with water, and brine
  9. dry with materialdried over magnesium sulfate
  10. customThe solvents were evaporated under the reduced pressure
  11. customThe residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-50% over 30 min with 0.1 M ammonium acetate, 21 mL/min)

Sources & evidence

ORD record
ord-4c605aa96fa0407fa6f22fb1fa6e3d6d
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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