3,4-dihydro-2H-pyran → 4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 1931604Notes

Reaction equation

HRID 1931604 reaction equation
[O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[Cl:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]2[NH:29][N:30]=[CH:31][C:24]=12.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[Cl:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]2[N:29]([CH:6]3[CH2:5][CH2:4][CH2:3][CH2:2][O:1]3)[N:30]=[CH:31][C:24]=12

Participants

6

Reactant 4

HCID 80803,4-dihydro-2H-pyranHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidine2×HCID 516892Sodium Bicarbonate

Product 1

HCID 2394984-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidineYield 80%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3,4-Dihydro-2H-pyran (10 mL) and 10-camphorsulfonic acid (200 mg, 0.86 mmol) were added to a solution of 4-chloro-1H-pyrazolo[3,4-d]pyrimidine (Intermediate 30; 2.1 g, 13.6 mmol) in ethyl acetate (80 mL). The mixture was stirred at room temperature for 70 h, poured into saturated aqueous sodium bicarbonate, and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography eluting with 20% ethyl acetate/hexanes to give 4-chloro-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (2.61 g, 80%) as a lavender-colored crystalline solid.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. custompurified by column chromatography
  7. washeluting with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f89dbd85b20f43ecb5cdd230b5125e4a
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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