Ethyl Acetate → 4-[4-(2-Methyl-pyridin-3-ylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931615Notes

Reaction equation

HRID 1931615 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].[NH2:24][C:25]1[C:26]([CH3:31])=[N:27][CH:28]=[CH:29][CH:30]=1.CC(C)([O-])C.[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]([NH:24][C:25]4[C:26]([CH3:31])=[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 5726163-Amino-2-methylpyridineHCID 23665647Potassium tert-butoxideHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 579650374-[4-(2-Methyl-pyridin-3-ylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 24.4%

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-amino-2-methylpyridine (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 21 mg, 0.19 mmol), and potassium tert-butoxide (22 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 twice with dichloromethane and the solvent was evaporated under high vacuum to give 4-[4-(2-methyl-pyridin-3-ylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (15 mg, 24%) as a white powder. Mass spectrum (ES) MH+=410. HRMS Calcd. for C21H28N7O2 (MH+): 410.2299. Found: 410.2299.

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-4676573eddb84c948136a446b88caacc
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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