Sodium hydride → HCID 57964957, compound

HRID 1931775Notes

Reaction equation

HRID 1931775 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[H-].[Na+].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([N:27]2[C:31]3=[N:32][C:33]([Cl:37])=[N:34][C:35](Cl)=[C:30]3[CH:29]=[N:28]2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>O1CCCC1>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([N:27]2[C:31]3=[N:32][C:33]([Cl:37])=[N:34][C:35]([O:11][C:8]4[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:6][CH:7]=4)=[C:30]3[CH:29]=[N:28]2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1233504-(Methylsulfonyl)phenolHCID 57964878HCID 57964878, compound2×

Product 1

HCID 57964957HCID 57964957, compoundYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-(methylsulfonyl)phenol (available from Matrix Scientific, Columbia, S.C., USA; 52 mg, 0.3 mmol) in tetrahydrofuran (3 mL) was cooled to 0° C. under argon. Sodium hydride (60% dispersion; 13.2 mg, 0.33 mmol) was added and the mixture was stirred for 10 min. 4-(4,6-Dichloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 24; 100 mg, 0.27 mmol) was added and the mixture was stirred at room temperature for 4 h and then poured into saturated aqueous ammonium chloride solution. The mixture was extracted three times with ethyl acetate and the combined organic layers were washed with brine, dried (magnesium sulfate), filtered, evaporated and purified by column chromatography, eluting with 25-50% ethyl acetate/hexanes to give 4-[6-chloro-4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (91 mg, 66%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 4 h
  2. extractionThe mixture was extracted three times with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by column chromatography
  8. washeluting with 25-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-a141a3563c134a8f8bb0a218f1afcc5e
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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