Potassium Hydroxide → (S)-3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1H-pyrazolo[3,4-d]pyrimidine

HRID 230189Notes

Reaction equation

HRID 230189 reaction equation
[OH-].[K+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[N:14][C:15](S(C)(=O)=O)=[N:16][C:17]=2[O:19][CH2:20][C@H:21]2[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22]2)[NH:12][N:11]=1.[F:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[OH:40]>>[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[N:14][C:15]([O:40][C:34]3[CH:35]=[CH:36][C:37]([F:39])=[CH:38][C:33]=3[F:32])=[N:16][C:17]=2[O:19][CH2:20][C@H:21]2[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22]2)[NH:12][N:11]=1

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 1230512,4-DifluorophenolHCID 178431483HCID 178431483, compound

Product 1

HCID 178431482(S)-3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1H-pyrazolo[3,4-d]pyrimidine

Conditions

Temperature
120 °C

Procedure

Powdered KOH (1.0 g) was taken up in 4 mL of 2,4-difluorophenol, and the resulting mixture was heated at 120° C. for 15 minutes. (S)-3-(2-Chloro-phenyl)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6-methylsulfonyl-1H-pyrazolo[3,4-d]pyrimidine (1.34 g, 0.305 mmol) was added, and the reaction mixture was stirred for one hour at 120° C. The reaction mixture was cooled to room temperature, partitioned between water (100 mL) and 15 EtOAc (300 mL0, and the layers were separated. The organic layer was washed three times with 2N aqueous NaOH, once with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative scale TLC (50% MeOH in methylene chloride to provide 1.395 mg of (S)-3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1H-pyrazolo[3,4-d]pyrimidine. Mass Spec. M+H=489. Mp.=70.1-75.9° C.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between water (100 mL) and 15 EtOAc (300 mL0
  3. customthe layers were separated
  4. washThe organic layer was washed three times with 2N aqueous NaOH
  5. dry with materialonce with brine, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative scale TLC (50% MeOH in methylene chloride

Sources & evidence

ORD record
ord-b7e34b466c114a98aa73451fc2f7a488
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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