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 1093173ノート

反応式

HRID 1093173 の反応式
[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

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

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)+

後処理

  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

出典と根拠

ORDレコード
ord-23a2af3ed96b4248a90a7ce8d139be83
出典データセット
uspto-grants-2012_03
特許番号
US08129371B2

反応ノート

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