p-Toluenesulfonic acid → 4-chloro-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 1811771Notes

Reaction equation

HRID 1811771 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]2[NH:9][N:10]=[CH:11][C:3]=12.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.CC1C=CC(S(O)(=O)=O)=CC=1>CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]2[N:9]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][O:12]3)[N:10]=[CH:11][C:3]=12

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 207959774-chloro-6-methyl-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 595482064-chloro-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidineYield 98.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of the above 4-chloro-6-methyl-1H-pyrazolo[3,4-d]pyrimidine (325 mg, 1928 μmol) in EtOAc (3 mL) was treated with 3,4-dihydro-2H-pyran (528 μL, 5783 μmol) and MP-TsOH resin (Biotage) (72 mg, 4.3 mmol/g, 0.15 eq) and the resulting suspension was heated at 90° C. for 3 h, after which time LCMS indicated essentially complete conversion. The solution was filtered, washed with EtOAc, and concentrated to give a pale yellow oil. Purification by flash chromatography (EtOAc/hexane; 5% to 20%) gave 4-chloro-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (482 mg, 98.9% yield) as a colorless oil. 1H NMR (400 MHz, d6-DMSO) δ 8.44 (s, 1H); 5.91-6.02 (m, 1H); 3.91-3.99 (m, 1H); 3.67-3.77 (m, 1H); 2.72 (s, 3H); 2.36-2.48 (m, 1H); 1.96-2.08 (m, 1H); 1.87-1.95 (m, 1H); 1.32-1.84 (m, 3H).

Workup

  1. filtrationThe solution was filtered
  2. washwashed with EtOAc
  3. concentrationconcentrated
  4. customto give a pale yellow oil
  5. customPurification by flash chromatography (EtOAc/hexane; 5% to 20%)

Sources & evidence

ORD record
ord-3955c64f6de142beaccfc1db2635e80a
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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