Ethyl Acetate → HCID 44514684, compound

HRID 1931703Notes

Reaction equation

HRID 1931703 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][S:25]([C:28]1[N:33]=[C:32]([CH3:34])[C:31]([OH:35])=[CH:30][CH:29]=1)(=[O:27])=[O:26].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:35][C:31]4[C:32]([CH3:34])=[N:33][C:28]([S:25]([CH3:24])(=[O:27])=[O:26])=[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 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×HCID 57964970HCID 57964970, compound2×

Product 1

HCID 44514684HCID 44514684, compoundYield 42%

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), 6-methanesulfonyl-2-methyl-pyridin-3-ol (Intermediate 6; 36 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 with dichloromethane and the solvent was evaporated to give 4-[4-(6-methanesulfonyl-2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (30 mg, 42%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.50 (s, 9H), 1.96-2.06 (m, 2H), 2.20-2.34 (m, 2H), 2.92-3.05 (m, 2H), 4.26-4.39 (m, 2H), 4.92-5.04 (m, 1H), 7.76 (d, 1H, J=8.4 Hz), 8.06 (d, 1H, J=8.4 Hz), 8.21 (s, 1H), 8.46 (s, 1H). Mass spectrum (ES) MH+=489. HRMS Calcd. for C22H29N6O5S (MH+): 489.1915. Found: 489.1915.

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 with dichloromethane
  7. customthe solvent was evaporated

Sources & evidence

ORD record
ord-0b4aeead2aab4204a55fbf946fcc11e3
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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