Acetone → (S)-3-iodo-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine acetate
Reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:12]3[CH2:17][CH2:16][CH2:15][N:14](C([O:20][C:21]([CH3:24])(C)C)=O)[CH2:13]3)[N:9]=[C:10]([I:11])[C:3]=12.Cl.CC(C)=[O:28]>>[C:21]([OH:20])(=[O:28])[CH3:24].[I:11][C:10]1[C:3]2[C:4](=[N:5][CH:6]=[N:7][C:2]=2[NH2:1])[N:8]([C@H:12]2[CH2:17][CH2:16][CH2:15][NH:14][CH2:13]2)[N:9]=1Participants
Conditions
- Temperature
- 45 °C
Procedure
To a mixture of (S)-tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (3.4 g, 0.0077 mol) in acetone (80 mL) was added an aqueous 6N solution of hydrogen chloride (20 mL) at room temperature. The mixture was stirred at 45° C. for 4 hours, then at room temperature for 18 hours. Acetone was removed under reduced pressure, and the aqueous layer was washed with toluene (2×20 mL) and dichloromethane (2×20 mL). The aqueous layer was basified with an aqueous 5N solution of sodium hydroxide (25 mL) at 0° C. The aqueous layers were concentrated to dryness, and the residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 2%-30% over 15 min with 0.1 M ammonium acetate, 21 mL/min) to yield (S)-3-iodo-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine acetate (0.75 g, 0.0019 mol).
Workup
- waitat room temperature for 18 hours
- customAcetone was removed under reduced pressure
- washthe aqueous layer was washed with toluene (2×20 mL) and dichloromethane (2×20 mL)
- customwas basified with an aqueous 5N solution of sodium hydroxide (25 mL) at 0° C
- concentrationThe aqueous layers were concentrated to dryness
- customthe residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 2%-30% over 15 min with 0.1 M ammonium acetate, 21 mL/min)
Sources & evidence
- ORD record
- ord-54a5ae95864240c4b81f74e98203ae84
- Source dataset
- uspto-grants-2005_07
- Patent number
- US06921763B2
Reaction notes
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