Trifluoroacetic acid → 3-(6-Chloro-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

HRID 1093173Notes

Reaction equation

HRID 1093173 reaction equation
[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[N:14]=[C:13]([Cl:15])[N:12]=[C:11]3[N:16]([CH:19]4[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=O)[CH2:21][CH2:20]4)[N:17]=[CH:18][C:10]=13)[CH2:2]2.[F:32][C:33]([F:38])([F:37])C(O)=O.FC(F)(F)C([O-])=O.ClC(Cl)(Cl)S(OCC(F)(F)F)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CC(C)=O>[Cl:15][C:13]1[N:12]=[C:11]2[N:16]([CH:19]3[CH2:24][CH2:23][N:22]([CH2:25][C:33]([F:38])([F:37])[F:32])[CH2:21][CH2:20]3)[N:17]=[CH:18][C:10]2=[C:9]([N:3]2[CH2:4][CH:5]3[O:8][CH:1]([CH2:7][CH2:6]3)[CH2:2]2)[N:14]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 84468TrifluoroacetateHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonateHCID 86629367tert-butyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate

Product 1

HCID 866293683-(6-Chloro-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Tert-butyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate (0.60 g, 1.3 mmol) was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (5 mL). When LC/MS analysis revealed the deprotection of the Boc group, the mixture was concentrated to dryness under reduced pressure. Diethyl ether was evaporated three times from the crude material in order to afford a solid residue. The trifluoroacetate salt was dissolved in approximately 15 mL of warm acetone and added to a 10-20 mL Smith process vial charged with 2,2,2-trifluoroethyl trichloromethanesulfonate (0.56 g, 2.0 mmol). Potassium carbonate (0.90 g, 6.5 mmol) was added and the suspension was heated in the microwave for one hour at 100° C. After cooling to room temperature, the mixture was concentrated to dryness under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure. 3-(6-Chloro-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane was thus obtained as a yellow foam (0.55 g, 100%). MS (ES+): 430.9, 432.9 (M+H)+

Workup

  1. concentrationthe mixture was concentrated to dryness under reduced pressure
  2. customDiethyl ether was evaporated three times from the crude material in order
  3. customto afford a solid residue
  4. additionadded to a 10-20 mL Smith process
  5. temperatureAfter cooling to room temperature
  6. concentrationthe mixture was concentrated to dryness under reduced pressure
  7. customThe residue was partitioned between ethyl acetate and water
  8. extractionThe aqueous phase was extracted three times with ethyl acetate
  9. washThe combined extracts were washed with saturated aqueous sodium chloride solution
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-23a2af3ed96b4248a90a7ce8d139be83
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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