Methanol → 6-(4-Acetyl-phenyl)-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

HRID 1693512Notes

Reaction equation

HRID 1693512 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[C:12](=[O:25])[C:13]3[CH:18]=[N:17][N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:14]=3[N:15]=2)=[CH:6][CH:5]=1.[OH-].[Na+].[CH3:36]O.[NH4+].[Cl-]>O1CCOCC1>[C:3]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[C:12](=[O:25])[C:13]3[CH:18]=[N:17][N:16]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:14]=3[N:15]=2)=[CH:6][CH:5]=1)(=[O:2])[CH3:36]

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 578981284-[5-(4-chloro-phenyl)-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-benzoic acid methyl ester

Product 1

HCID 116765606-(4-Acetyl-phenyl)-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-[5-(4-chloro-phenyl)-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-benzoic acid methyl ester (450 mg, 0.98 mmol) in dioxane (6 mL) is added NaOH (2 N, 1.5 mL, 3 mmol) and stirred at room temperature for 14 h. The mixture is then concentrated and treated with SOCl2 (4 mL) at room temperature for 1 h. The excess SOCl2 is removed under vacuum and flushed with toluene (2×2 mL). The resulted residue is dissolved in CH2Cl2 (3 mL) and slowly dropped into a solution of freshly prepared Me2CuLi (2.0 mmol) in Et20 (4 mL) at −78° C. The mixture is kept at the same temperature for 1 h. when MeOH (1 mL) is added to quench the reaction. The mixture is then allowed to warm up to room temperature and treated with saturated aqueous NH4Cl solution (20 mL). After extraction with EtOAc(3×15 mL), the organic layers are combined, washed with brine and dried (MgSO4). After filtering off the drying agent, the solvent is removed under vacuum and the residue is purified by flash column chromatography (silica gel, 0%˜50% EtOAc/hexane) to provide the titled compound 6-(4-acetyl-phenyl)-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one. HPLC-MS calculated for C25H17ClN4O2 (M+H+): 441.1. Found: 441.1.

Workup

  1. concentrationThe mixture is then concentrated
  2. additiontreated with SOCl2 (4 mL) at room temperature for 1 h
  3. customThe excess SOCl2 is removed under vacuum
  4. customflushed with toluene (2×2 mL)
  5. dissolutionThe resulted residue is dissolved in CH2Cl2 (3 mL)
  6. additionslowly dropped into a solution
  7. customof freshly prepared Me2CuLi (2.0 mmol) in Et20 (4 mL) at −78° C
  8. waitThe mixture is kept at the same temperature for 1 h.
  9. customto quench
  10. customthe reaction
  11. temperatureto warm up to room temperature
  12. extractionAfter extraction with EtOAc(3×15 mL)
  13. washwashed with brine
  14. dry with materialdried (MgSO4)
  15. filtrationAfter filtering off the drying agent
  16. customthe solvent is removed under vacuum
  17. customthe residue is purified by flash column chromatography (silica gel, 0%˜50% EtOAc/hexane)

Sources & evidence

ORD record
ord-11dfb4e4052540bea4fd2ec17d8ce17e
Source dataset
uspto-grants-2012_04
Patent number
US08158634B2

Reaction notes

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