2,4-Dichlorophenol → HCID 57965056, compound

HRID 1931645Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22](Cl)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[Cl:30][C:31]1[CH:36]=[C:35]([Cl:37])[CH:34]=[CH:33][C:32]=1[OH:38]>CN1CCCC1=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:38][C:32]4[CH:33]=[CH:34][C:35]([Cl:37])=[CH:36][C:31]=4[Cl:30])=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 42 mg, 0.12 mmol), anhydrous potassium carbonate (22 mg, 0.16 mmol) and 2,4-dichlorophenol (26 mg, 0.16 mmol) in N-methylpyrrolidinone (0.5 mL) was heated to 100° C. in a sealed scintillation vial. After 18 hr, the mixture was allowed to cool to room temperature and the reaction mixture purified by reverse phase HPLC to give 4-[4-(2,4-dichloro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (8 mg, 14%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.97-2.05 (m, 2H), 2.18-2.33 (m, 2H), 2.90-3.04 (m, 2H), 4.24-4.40 (m, 2H), 4.90-5.02 (m, 1H), 7.23-7.25 (m, 1H), 7.36 (dd, 1H, J=8.6, 2.6 Hz), 7.64 (d, 1H, J=2.1 Hz), 8.12 (s, 1H), 8.49 (s, 1H). Mass spectrum MH+=464.

Workup

temperatureto cool to room temperature
customthe reaction mixture purified by reverse phase HPLC

Sources & evidence

ORD record: ord-90e0e4b4ecaa40109fae3c55c2d65f16
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188098B2

Reaction notes

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