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

HRID 1926113Notes

Reaction equation

HRID 1926113 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][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=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][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:43])([F:44])[F:42])[CH:36]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 10176127Pyridinium chlorideHCID 196269843-Chloro-4-[3-(trifluoromethyl)phenoxy]anilineHCID 675208502-{2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethoxy}ethyl benzoate

Product 1

HCID 575972042-{2-[7-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethoxy}ethanolYield 11.1%

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 (328 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (264 mg), pyridine hydrochloride (159 mg) and 1-methyl-2-pyrrolidone (7.5 mL) was stirred at 140° C. for 33.5 hrs. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate (15 mL), and extracted with ethyl acetate (35 mL×2). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100). 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 2 hrs. After concentration of the reaction mixture under reduced pressure, water (30 mL) was added, and the mixture was extracted with ethyl acetate (40 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 ethyl acetate-hexane to give the title compound (50 mg).

Workup

  1. extractionextracted with ethyl acetate (35 mL×2)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationAfter concentration under reduced pressure
  4. concentrationThe object fraction was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in methanol (5 mL)
  6. addition1N Aqueous sodium hydroxide solution (1 mL) was added
  7. stirringthe mixture was stirred at room temperature for 2 hrs
  8. additionAfter concentration of the reaction mixture under reduced pressure, water (30 mL) was added
  9. extractionthe mixture was extracted with ethyl acetate (40 mL×2)
  10. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100)
  13. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-78306d475e434abb9d23e33dd326dc77
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

Loading…