Potassium Carbonate → 3-chloro-N-[3-(4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-ylmethoxy)-4-methyl-phenyl]-4-fluoro-benzamide

HRID 2426133Notes

Reaction equation

HRID 2426133 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([OH:15])[CH:9]=1)=[O:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:27][C:28]1[C:36]2[C:31](=[N:32][CH:33]=[N:34][C:35]=2[Cl:37])[N:30]([CH3:38])[N:29]=1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([O:15][CH2:27][C:28]2[C:36]3[C:31](=[N:32][CH:33]=[N:34][C:35]=3[Cl:37])[N:30]([CH3:38])[N:29]=2)[CH:9]=1)=[O:6]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 575815783-chloro-4-fluoro-N-(3-hydroxy-4-methyl-phenyl)-benzamideHCID 575815813-bromomethyl-4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 575815883-chloro-N-[3-(4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-ylmethoxy)-4-methyl-phenyl]-4-fluoro-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-chloro-4-fluoro-N-(3-hydroxy-4-methyl-phenyl)-benzamide (105.9 mg, 0.379 mmol) and potassium carbonate (59.6 mg, 0.431 mmol) in dimethylformamide was stirred at room temperature for 30 minutes before 3-bromomethyl-4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (90.7 mg, 0.347 mmol, Example 5) was added. The reaction was stirred at room temperature overnight and then concentrated under reduced pressure to remove dimethylformamide. The residue was dissolved in ethyl acetate, washed with water, dried and concentrated. The crude product was either used directly for the next step or purified by flash chromatography (silica gel, hexanes-ethyl acetate, 90/10 to 50/50) to give pure 3-chloro-N-[3-(4-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-ylmethoxy)-4-methyl-phenyl]-4-fluoro-benzamide as a white solid. (Yield 35.5 mg).

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. customto remove dimethylformamide
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water
  6. customdried
  7. concentrationconcentrated
  8. custompurified by flash chromatography (silica gel, hexanes-ethyl acetate, 90/10 to 50/50)

Sources & evidence

ORD record
ord-6568c3220c844d658f8f7f4e978a2940
Source dataset
uspto-grants-2011_06
Patent number
US07968554B2

Reaction notes

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