Cesium carbonate → tert-Butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)azetane-1-carboxylate

HRID 897902Notes

Reaction equation

HRID 897902 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.CS(O[CH:17]1[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18]1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:17]3[CH2:18][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20]3)[N:3]=[C:2]([I:1])[C:10]=12

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 10753243Tert-butyl 3-(methanesulfonyloxy)azetidine-1-carboxylate2×HCID 178508725HCID 178508725, compound

Product 1

HCID 22346992tert-Butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)azetane-1-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.73 g, 0.0028 mol), tert-butyl 3-[(methylsulfonyl)oxy]-1-azetanecarboxylate (1.05 g, 0.0042 mol) and cesium carbonate (1.4 g, 0.0042 mol) in N,N-dimethylformamide (25 mL) were stirred at 70° C. under an atmosphere of nitrogen for 16 hours. The mixture was cooled to room temperature. Additional tert-butyl 3-[(methylsulfonyl)oxy]-1-azetanecarboxylate (0.35 g, 0.0014 mol) and cesium carbonate (0.46 g, 0.0014 mol) were added to the mixture. The mixture was stirred at 70° C. under an atmosphere of nitrogen for 16 hours. The solvent was removed under the reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with dichloromethane (3×70 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 triturated with dichloromethane (2×3 mL) to give tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-azetanecarboxylate (0.57 g, 0.0014 mol).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. stirringThe mixture was stirred at 70° C. under an atmosphere of nitrogen for 16 hours
  3. customThe solvent was removed under the reduced pressure
  4. customThe residue was partitioned between water and ethyl acetate
  5. extractionThe aqueous layer was extracted with dichloromethane (3×70 mL)
  6. washThe combined organic extracts were washed with water, and brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvents were evaporated under the reduced pressure
  9. customThe residue was triturated with dichloromethane (2×3 mL)

Sources & evidence

ORD record
ord-c1ec6c25743d422f98ffbf6b8fda50a9
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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