Sodium Bicarbonate → 2-{2-[7-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethoxy}ethanol

HRID 1926112Notes

Reaction equation

HRID 1926112 reaction equation
C([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:22](SC)=[N:21][CH:20]=[N:19][C:18]=2[CH:17]=[N:16]1)(=O)C1C=CC=CC=1.[Cl:26][C:27]1[CH:28]=[C:29]([CH:31]=[CH:32][C:33]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=1)[NH2:30].Cl.N1C=CC=CC=1.C(=O)([O-])O.[Na+]>CN1CCCC1=O>[Cl:26][C:27]1[CH:28]=[C:29]([NH:30][C:22]2[C:23]3[N:15]([CH2:14][CH2:13][O:12][CH2:11][CH2:10][OH:9])[N:16]=[CH:17][C:18]=3[N:19]=[CH:20][N:21]=2)[CH:31]=[CH:32][C:33]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 10176127Pyridinium chlorideHCID 675208502-{2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethoxy}ethyl benzoate

Product 1

HCID 575972702-{2-[7-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethoxy}ethanolYield 30.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-{2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethoxy}ethyl benzoate (200 mg), 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (140 mg), pyridine hydrochloride (96 mg) and 1-methyl-2-pyrrolidone (5 mL) was stirred at 140° C. for 16.5 hrs. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate (30 mL), and extracted with ethyl acetate (30 mL×3). The organic layers were combined, washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=90:10→20:80). The object fraction was concentrated under reduced pressure and the residue was dissolved in methanol (5 mL). 1N Aqueous sodium hydroxide solution (1 mL) was added and the mixture was stirred at room temperature for 11.5 hrs. After concentration of the reaction mixture under reduced pressure, water (30 mL) was added, and the mixture was extracted with ethyl acetate (45 mL×2). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100) and recrystallized from ethanol-ethyl acetate to give the title compound (78 mg).

Workup

  1. extractionextracted with ethyl acetate (30 mL×3)
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. concentrationThe object fraction was concentrated under reduced pressure
  6. dissolutionthe residue was dissolved in methanol (5 mL)
  7. addition1N Aqueous sodium hydroxide solution (1 mL) was added
  8. stirringthe mixture was stirred at room temperature for 11.5 hrs
  9. additionAfter concentration of the reaction mixture under reduced pressure, water (30 mL) was added
  10. extractionthe mixture was extracted with ethyl acetate (45 mL×2)
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100)
  14. customrecrystallized from ethanol-ethyl acetate

Sources & evidence

ORD record
ord-4372803a3be945fcb2832b7852bb2f3d
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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