Hydrochloric Acid → 5-(4-Chloro-phenyl)-6-[4-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

HRID 1693508Notes

Reaction equation

HRID 1693508 reaction equation
CO[C:3](=[O:33])[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+].Cl.O[NH:38][C:39](=[NH:41])[CH3:40].CCN(CC)CC>O1CCOCC1.O>[Cl:32][C:29]1[CH:28]=[CH:27][C:26]([N:11]2[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]=[C:10]2[C:7]2[CH:6]=[CH:5][C:4]([C:3]3[O:33][N:41]=[C:39]([CH3:40])[N:38]=3)=[CH:9][CH:8]=2)=[CH:31][CH:30]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 578981284-[5-(4-chloro-phenyl)-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-benzoic acid methyl esterHCID 178465666HCID 178465666, compound

Product 1

HCID 116343785-(4-Chloro-phenyl)-6-[4-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 (50 mg, 0.11 mmol) in dioxane is added NaOH (1N, 400 μL, 0.4 mmol) and stirred at room temperature for 14 h. The mixture is then neutralized by adding HCl (1N, 400 μL, 0.4 mmol) and concentrated. The resulted residue is treated with SOCl2 (1 mL) at room temperature for 1 h and excess SOCl2 is removed under vacuum. The residue is dissolved in CH2Cl2 and added N-hydroxy-acetamidine (12 mg, 0.16 mmol) followed by Et3N (17 mg, 0.16 mmol). After stirring at room temperature for 1 h, the mixture is treated with water (2 mL) and extracted with EtOAc (3×2 mL). The organic layers are combined and concentrated, the residue is dissolved in EtOH (4 mL), NaOAc (40 mg) is added and the mixture is heated to 80° C. for 5 h. After cooling down to room temperature, the solvent is removed and the residue is purified by preparative LC/MS to provide the titled compound 5-(4-chloro-phenyl)-6-[4-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one. 1H NMR (CDCl3) δ(ppm) 8.35(s, 1H), 8.12(d, 2H), 8.01(d, 2H), 7.48-7.54 (m, 4H), 7.37 (t, 1H), 7.32(d, 2H), 7.10(d, 2H), 2.47(s, 3H); HPLC-MS calculated for C26H17ClN6O2 (M+H+): 481.1. Found: 481.1.

Workup

  1. concentrationconcentrated
  2. additionThe resulted residue is treated with SOCl2 (1 mL) at room temperature for 1 h
  3. customexcess SOCl2 is removed under vacuum
  4. dissolutionThe residue is dissolved in CH2Cl2
  5. stirringAfter stirring at room temperature for 1 h
  6. extractionextracted with EtOAc (3×2 mL)
  7. concentrationconcentrated
  8. dissolutionthe residue is dissolved in EtOH (4 mL)
  9. additionNaOAc (40 mg) is added
  10. temperaturethe mixture is heated to 80° C. for 5 h
  11. temperatureAfter cooling down to room temperature
  12. customthe solvent is removed
  13. customthe residue is purified by preparative LC/MS

Sources & evidence

ORD record
ord-b4a36166a3fc49a7b95ed3bf630f5472
Source dataset
uspto-grants-2012_04
Patent number
US08158634B2

Reaction notes

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