Water → HCID 57964969, compound

HRID 1931721Notes

Reaction equation

HRID 1931721 reaction equation
[H-].[Na+].[N+](C1[CH:11]=[CH:10][C:9]([O:12][C:13]([N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[C:25]4=[N:26][CH:27]=[N:28][C:29]([O:30][C:31]5[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=5)=[C:24]4[CH:23]=[N:22]3)[CH2:17][CH2:16]2)=[O:14])=[CH:8]C=1)([O-])=O.C1(O)CCC1.O>O1CCCC1>[CH:9]1([O:12][C:13]([N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[C:25]4=[N:26][CH:27]=[N:28][C:29]([O:30][C:31]5[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=5)=[C:24]4[CH:23]=[N:22]3)[CH2:17][CH2:16]2)=[O:14])[CH2:10][CH2:11][CH2:8]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 57964982HCID 57964982, compound

Product 1

HCID 57964969HCID 57964969, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in oil; 10 mg, 0.25 mmol) was added to a solution of 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 4-nitro-phenyl ester (Example 123; 60 mg, 0.13 mmol) in anhydrous tetrahydrofuran (1 mL) under argon. The mixture was stirred for 5 min and then cyclobutanol (11 μL, 0.14 mmol) was added and the mixture was stirred at room temperature for 7 h. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried (sodium sulfate), filtered, evaporated, and purified on a Silicycle 4 g column, eluting with 0-4% methanol/dichloromethane to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclobutyl ester (7 mg, 14%).

Workup

  1. stirringthe mixture was stirred at room temperature for 7 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified on a Silicycle 4 g column
  8. washeluting with 0-4% methanol/dichloromethane

Sources & evidence

ORD record
ord-3edb62eec6654718af09f6092b5aa661
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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