Dichloromethane → HCID 53257684, compound

HRID 1931646Notes

Reaction equation

HRID 1931646 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].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>CN(C)C=O.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:32][C:29]4[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 90154-MethoxyphenolHCID 11430Potassium CarbonateHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 53257684HCID 53257684, compoundYield 29.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 50 mg, 0.15 mmol), 4-methoxy-phenol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 24 mg, 0.19 mmol), and potassium carbonate (27 mg, 0.2 mmol) in dimethylformamide (2 mL) was heated in the microwave oven at 160° C. for 10 min. Dichloromethane and water were added, and the dichloromethane layer was washed twice with water. The dichloromethane layer was evaporated, and purified by preparative C18 HPLC, eluting with 25-100% acetonitrile/water to give 4-[4-(4-methoxy-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (19 mg, 28%) as an off-white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.95-2.02 (m, 2H), 2.16-2.30 (m, 2H), 2.90-3.04 (m, 2H), 3.85 (s, 3H), 4.22-4.37 (m, 2H), 4.88-4.99 (m, 1H), 6.98 (d, 1H, J=8.7 Hz), 7.16 (d, 1H, J=8.9 Hz), 7.77 (s, 1H), 8.54 (s, 1H). Mass spectrum MH+=426. HRMS Calcd. For C22H28N5O4 (MH+): 426.2136. Found: 426.2134.

Workup

  1. washthe dichloromethane layer was washed twice with water
  2. customThe dichloromethane layer was evaporated
  3. custompurified by preparative C18 HPLC
  4. washeluting with 25-100% acetonitrile/water

Sources & evidence

ORD record
ord-727e38dc3c464ebba4a405c177523939
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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