Ethyl Acetate → HCID 66915356, compound

HRID 1931647Notes

Reaction equation

HRID 1931647 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].[CH2:24]([O:26][C:27]1[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=1)[CH3:25].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>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:33][C:30]4[CH:31]=[CH:32][C:27]([O:26][CH2:24][CH3:25])=[CH:28][CH:29]=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 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 121504-EthoxyphenolHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 66915356HCID 66915356, compoundYield 52%

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-ethoxyphenol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 27 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. Ethyl acetate and water were added, and the aqueous layer was extracted twice with ethyl acetate. The ethyl acetate layers were combined, evaporated, and purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water. Samples containing the product were extracted twice with dichloromethane and the solvent was evaporated under high vacuum to give 4-[4-(4-ethoxy-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (34 mg, 52%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.44 (t, 3H, J=7.0 Hz), 1.49 (s, 9H), 1.96-2.05 (m, 2H), 2.17-2.30 (m, 1H), 2.86-3.04 (m, 2H), 4.06 (q, 2H, J=6.9 Hz), 4.23-4.36 (m, 2H), 4.90-5.00 (m, 1H), 6.97 (d, 2H, J=8.8 Hz), 7.15 (d, 2H, J=9.0 Hz), 8.54 (s, 1H), 8.54 (s, 1H). Mass spectrum (ES) MH+=440. HRMS Calcd. for C23H30N5O4 (MH+): 440.2293. Found: 440.2292.

Workup

  1. extractionthe aqueous layer was extracted twice with ethyl acetate
  2. customevaporated
  3. custompurified by preparative C18 HPLC
  4. washeluting with 10-100% acetonitrile/water
  5. additionSamples containing the product
  6. extractionwere extracted twice with dichloromethane
  7. customthe solvent was evaporated under high vacuum

Sources & evidence

ORD record
ord-92c1a320fe9f48c6b8180cc8d54a825c
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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