Sodium hydride → 3-(1-(6-Phenoxy-pyridin-3-ylmethyl)-1H-pyrazol-4-yl)-pyridin-2-ylamine

HRID 78203Notes

Reaction equation

HRID 78203 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:3]=[N:2]1.[H-].[Na+].Cl[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:21][CH:22]=1>CN(C)C=O>[O:23]([C:20]1[N:21]=[CH:22][C:17]([CH2:16][N:1]2[CH:5]=[C:4]([C:6]3[C:7]([NH2:12])=[N:8][CH:9]=[CH:10][CH:11]=3)[CH:3]=[N:2]2)=[CH:18][CH:19]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 132534765-Chloromethyl-2-phenoxy-pyridineHCID 592552903-(1H-pyrazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 592552213-(1-(6-Phenoxy-pyridin-3-ylmethyl)-1H-pyrazol-4-yl)-pyridin-2-ylamineYield 58.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an N,N-dimethylformamide (5.00 mL) solution of 3-(1H-pyrazol-4-yl)-pyridin-2-ylamine (20.0 mg, 0.125 mmol) described in Manufacturing Example 32-1-4 was added sodium hydride (5.50 mg, 0.138 mmol, 60% in oil) on an ice bath (0° C.) under nitrogen atmosphere, which was stirred for 10 minutes at room temperature. Thereafter, 5-chloromethyl-2-phenoxy-pyridine (49.7 mg, 0.226 mmol) described in Manufacturing Example 193-1-2 was added to the above mixture, which was stirred for 30 minutes at room temperature. The reaction mixture was partitioned into ethyl acetate and water at room temperature. The organic layer was washed with water and saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=2:1→ethyl acetate) to obtain the title compound (25.0 mg, 58.2%).

Workup

  1. additionwas added to the above mixture, which
  2. stirringwas stirred for 30 minutes at room temperature
  3. customThe reaction mixture was partitioned into ethyl acetate and water at room temperature
  4. washThe organic layer was washed with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under a reduced pressure
  7. customThe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=2:1→ethyl acetate)

Sources & evidence

ORD record
ord-1d9f71bd7387415092333e5b812ccaa6
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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