Tetrahydrofuran → 2-allyl-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-1-[6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one

HRID 1630388Notes

Reaction equation

HRID 1630388 reaction equation
C(N(CC)CC)C.Cl[CH2:9][CH2:10][CH2:11][C:12](Cl)=[O:13].O1CCCC1.[CH2:20]([N:23]1[C:31](=[O:32])[C:30]2[C:25](=[N:26][C:27]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([N:40]4[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]4)=[CH:36][CH:35]=3)=[N:28][CH:29]=2)[N:24]1[C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([NH2:53])[N:48]=1)[CH:21]=[CH2:22]>O>[CH2:20]([N:23]1[C:31](=[O:32])[C:30]2[C:25](=[N:26][C:27]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([N:40]4[CH2:41][CH2:42][N:43]([CH3:46])[CH2:44][CH2:45]4)=[CH:36][CH:35]=3)=[N:28][CH:29]=2)[N:24]1[C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([N:53]2[CH2:9][CH2:10][CH2:11][C:12]2=[O:13])[N:48]=1)[CH:21]=[CH2:22]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 53344705HCID 53344705, compound2×

Product 1

HCID 248564402-allyl-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-1-[6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-oneYield 21.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

With cooling with ice, 0.012 mL of triethylamine and 12.4 mg of 4-chlorobutyric acid chloride were added to tetrahydrofuran (1 mL) solution of 20 mg of the compound obtained in Example 50, 2-allyl-1-(6-aminopyridin-2-yl)-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one, and stirred at room temperature for 1 hour. Water was added to the reaction mixture, extracted with chloroform, and the organic layer was washed with saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, the resulting residue was dissolved in 1 mL of N,N-dimethylformamide, and 5 mg of potassium tert-butoxide was added thereto and stirred at room temperature for 30 minutes. Saturated ammonium chloride solution was added to the reaction mixture, extracted with ethyl acetate, and the organic layer was washed with saturated saline water and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through preparative thin-layer chromatography (chloroform/methanol=10/1) to obtain 5 mg of the entitled compound as a yellow solid.

Workup

  1. extractionextracted with chloroform
  2. washthe organic layer was washed with saturated saline water
  3. dry with materialdried with anhydrous sodium sulfate
  4. customThe solvent was evaporated away under reduced pressure
  5. dissolutionthe resulting residue was dissolved in 1 mL of N,N-dimethylformamide
  6. addition5 mg of potassium tert-butoxide was added
  7. stirringstirred at room temperature for 30 minutes
  8. additionSaturated ammonium chloride solution was added to the reaction mixture
  9. extractionextracted with ethyl acetate
  10. washthe organic layer was washed with saturated saline water
  11. dry with materialdried with anhydrous sodium sulfate
  12. customThe solvent was evaporated away under reduced pressure
  13. customthe resulting residue was purified through preparative thin-layer chromatography (chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-a3b117874e3e4d04a80c5a2c90d5014f
Source dataset
uspto-grants-2014_07
Patent number
US08791125B2

Reaction notes

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