Ethyl Acetate → HCID 57964952, compound

HRID 1931704Notes

Reaction equation

HRID 1931704 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:24]([C:26]1[C:31]([OH:32])=[CH:30][CH:29]=[CH:28][N:27]=1)#[N: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:32][C:31]4[C:26]([C:24]#[N:25])=[N:27][CH:28]=[CH:29][CH:30]=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 1019203-Hydroxypyridine-2-carbonitrileHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 57964952HCID 57964952, compoundYield 59%

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), 2-cyano-3-hydroxypyridine (Matrix Scientific, Columbia, S.C., USA; 26 mg, 0.19 mmol), and potassium carbonate (27 mg, 0.19 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 three times with dichloromethane and the solvent was evaporated to give 4-[4-(2-cyano-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (37 mg, 59%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.51 (s, 9H), 1.85-2.11 (m, 2H), 2.15-2.43 (m, 2H), 2.85-3.15 (m, 2H), 4.34 (br s, 2H), 4.88-5.09 (m, 1H), 7.68 (dd, 1H, J=8.4, 4.7 Hz), 7.88 (d, 1H, J=8.4 Hz), 8.27 (s, 1H), 8.49 (s, 1H), 8.69 (d, 1H, J=4.7 Hz). Mass spectrum (ES) MH+=422. HRMS Calcd. for C21H24N7O3 (MH+): 422.1935. Found: 422.1934.

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 three times with dichloromethane
  7. customthe solvent was evaporated

Sources & evidence

ORD record
ord-f4e4732293be4dc0ad495536a1207116
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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