Methyl iodide → [1-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-methyl-amine

HRID 451217Notes

Reaction equation

HRID 451217 reaction equation
C(O[C:6](=O)[NH:7][C:8]1[C:9]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])=[C:10]2[CH:16]=[N:15][N:14]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:11]2=[N:12][CH:13]=1)(C)(C)C.[H-].[Na+].IC>CN(C=O)C>[CH2:17]([N:14]1[C:11]2=[N:12][CH:13]=[C:8]([NH:7][CH3:6])[C:9]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[CH3:31])=[C:10]2[CH:16]=[N:15]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67440908[1-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-carbamic acid tert-butyl ester

Product 1

HCID 67441403[1-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-methyl-amineYield 107.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [1-benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-carbamic acid tert-butyl ester (2.6 g, 6.01 mmol) in DMF (50 mL) at 0° C. was added NaH (0.462 g, 50% purity, 9.62 mmol). After 20 minutes, iodomethane (1.54 g, 10.8 mmol) was added and the temperature raised to RT. The reaction was quenched by addition of H2O and the product extracted with EtOAc. The combined organic phases were dried over Na2SO4, and concentrated under vacuo to give a crude intermediate which was used directly in the next step without further purification. This residue as dissolved in CH2Cl2 (50 mL) and TFA (15 mL) was added. The reaction mixture was heated at 30° C. for 2 hours, diluted with CH2Cl2 (100 mL) and aqueous NaOH (1N) was added until pH reached 8. The organic phase was dried over Na2SO4, concentrated under vacuo to give the title product 2.24 g (97%) with high purity (no further purification needed) as a light yellow solid. ES-MS m/e: 347.3 (M+H+).

Workup

  1. customThe reaction was quenched by addition of H2O
  2. extractionthe product extracted with EtOAc
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. concentrationconcentrated under vacuo
  5. customto give a crude intermediate which
  6. customwas used directly in the next step without further purification
  7. dissolutionThis residue as dissolved in CH2Cl2 (50 mL)
  8. additionTFA (15 mL) was added
  9. temperatureThe reaction mixture was heated at 30° C. for 2 hours
  10. additiondiluted with CH2Cl2 (100 mL) and aqueous NaOH (1N)
  11. additionwas added until pH
  12. dry with materialThe organic phase was dried over Na2SO4
  13. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-3d8f70566cd84aa3bdc68fa3f5d08a6d
Source dataset
uspto-grants-2013_07
Patent number
US08487102B2

Reaction notes

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