Ethyl Acetate → HCID 57965027, compound

HRID 1931707Notes

Reaction equation

HRID 1931707 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].[OH:24][C:25]1[CH:30]=[CH:29][C:28](=[O:31])[N:27]([CH3:32])[N:26]=1.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:24][C:25]4[CH:30]=[CH:29][C:28](=[O:31])[N:27]([CH3:32])[N:26]=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 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×HCID 178481946HCID 178481946, compound

Product 1

HCID 57965027HCID 57965027, compoundYield 39%

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), 3-hydroxy-1-methylpyridazin-6(1H)-one (Oakwood Products, Inc., West Columbia, S.C., 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. Ethyl acetate and water were added, and the aqueous layer was extracted three times 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-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (25 mg, 39%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.95-2.04 (m, 2H), 2.20-2.36 (m, 2H), 2.92-3.05 (m, 2H), 3.76 (s, 3H), 4.26-4.40 (m, 2H), 4.90-5.02 (m, 1H), 7.07 (d, 1H, J=9.7 Hz), 7.24 (d, 1H, J=9.7 Hz), 8.17 (s, 1H), 8.51 (s, 1H). Mass spectrum (ES) MH+=428. HRMS Calcd. for C20H26N7O4 (MH+): 428.2041. Found: 428.2040.

Workup

  1. extractionthe aqueous layer was extracted three times 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-9a14403922c84b20ad0cf768592d791d
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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