Methyl iodide → N-benzyl-N-methyl-6-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[3,2-b]pyridin-1-amine

HRID 1404613Notes

Reaction equation

HRID 1404613 reaction equation
[CH2:1]([NH:8][N:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[N:20][N:21]([CH:23]4[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]4)[CH:22]=3)[CH:16]=2)[CH:11]=[CH:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:38]I>CN(C=O)C>[CH2:1]([N:8]([CH3:38])[N:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[N:20][N:21]([CH:23]4[CH2:24][CH2:25][NH:26][CH2:27][CH2:28]4)[CH:22]=3)[CH:16]=2)[CH:11]=[CH:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67458095tert-butyl 4-{4-[1-(benzylamino)-1H-pyrrolo[3,2-b]pyridin-6-yl]-1H-pyrazol-1-yl}piperidine-1-carboxylate

Product 1

HCID 58532365N-benzyl-N-methyl-6-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[3,2-b]pyridin-1-amineYield 4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 4-{4-[1-(benzylamino)-1H-pyrrolo[3,2-b]pyridin-6-yl]-1H-pyrazol-1-yl}piperidine-1-carboxylate (prepared in example 25: 125 mg, 0.26 mmol) in 3.0 mL of DMF at 0° C. was added NaH (60% in oil, 31 mg, 0.78 mmol) in one portion. After 15 min, the mixture was treated with methyl iodide. HPLC check shows disappearance of starting material. Solvent was removed and the residue dissolved in ethyl acetate, washed with aqueous NaHCO3. The organic solution was dried, evaporated and then the residue was treated with methanol (0.5 mL) and HCl (4.0M in dioxane, 2.0 mL) at room temperature for 30 min. The solvent was removed and the residue was purified by preparative HPLC to give product as a white solid (4.1 mg, yield 4%).

Workup

  1. customSolvent was removed
  2. dissolutionthe residue dissolved in ethyl acetate
  3. washwashed with aqueous NaHCO3
  4. customThe organic solution was dried
  5. customevaporated
  6. additionthe residue was treated with methanol (0.5 mL) and HCl (4.0M in dioxane, 2.0 mL) at room temperature for 30 min
  7. customThe solvent was removed
  8. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-717f971736a14d6aad81ef53f1d773eb
Source dataset
uspto-grants-2014_12
Patent number
US08912330B2

Reaction notes

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