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Water → 4-[4-(2,4,5-Trifluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931643
Notes
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Reaction equation

HRID 1931643 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([N:20]2[C:24]3=[N:25][CH:26]=[N:27][C:28](Cl)=[C:23]3[CH:22]=[N:21]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[F:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[OH:39].O>CN(C)C=O.C(OCC)C>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([N:20]2[C:24]3=[N:25][CH:26]=[N:27][C:28]([O:39][C:32]4[CH:33]=[C:34]([F:38])[C:35]([F:37])=[CH:36][C:31]=4[F:30])=[C:23]3[CH:22]=[N:21]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 1231532,4,5-TrifluorophenolHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 579648894-[4-(2,4,5-Trifluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Potassium carbonate (53 mg, 0.39 mmol) was added to a solution of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 100 mg, 0.3 mmol) and 2,4,5-trifluoro-phenol (available from Alfa Aesar, Ward Hill, Mass., USA; 57 mg, 0.39 mmol) in dimethylformamide (5 mL). The reaction mixture was heated at 100° C. in an oil bath overnight, then it was cooled to room temperature, and water and diethyl ether were added. The aqueous phase was extracted twice with diethyl ether and three times with hexane. The combined organic phases were evaporated and the resulting residue was purified by C18 reversed phase HPLC using a gradient of 20-100% acetonitrile/water to give 4-[4-(2,4,5-trifluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (66 mg, 50%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.95-2.06 (m, 2H), 2.18-2.34 (m, 2H), 2.90-3.06 (m, 2H), 4.26-4.38 (m, 2H), 4.90-5.02 (m, 1H), 7.09-7.21 (m, 2H), 8.16 (s, 1H), 8.49 (s, 1H). HRMS Calcd. for C21H23F3N5O3 (MH+): 450.1748. Found: 450.1745.

Workup

  1. temperatureit was cooled to room temperature
  2. extractionThe aqueous phase was extracted twice with diethyl ether and three times with hexane
  3. customThe combined organic phases were evaporated
  4. customthe resulting residue was purified by C18 reversed phase HPLC

Sources & evidence

ORD record
ord-64032aa69c4a4c91a9a1f3c64b5fd771
Source dataset
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08188098B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes