Sodium hydride → 3-(1-(4-(Pyridin-2-yloxymethyl)-benzyl)-1H-pyrazol-4-yl)-pyridin-2,6-diamine

HRID 1891598Notes

Reaction equation

HRID 1891598 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([NH2:13])=[N:8][C:9]([NH2:12])=[CH:10][CH:11]=2)[CH:3]=[N:2]1.[H-].[Na+].Cl[CH2:17][C:18]1[CH:31]=[CH:30][C:21]([CH2:22][O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)=[CH:20][CH:19]=1>CN(C)C=O>[N:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[O:23][CH2:22][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][N:1]2[CH:5]=[C:4]([C:6]3[C:7]([NH2:13])=[N:8][C:9]([NH2:12])=[CH:10][CH:11]=3)[CH:3]=[N:2]2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 592550952-(4-Chloromethyl-benzyloxy)-pyridineHCID 592551723-(1H-pyrazol-4-yl)-pyridine-2,6-diamine

Product 1

HCID 592553263-(1-(4-(Pyridin-2-yloxymethyl)-benzyl)-1H-pyrazol-4-yl)-pyridin-2,6-diamineYield 43.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1H-pyrazol-4-yl)-pyridin-2,6-diamine (25 mg, 0.14 mmol) described in Manufacturing Example 36-1-2 in N,N-dimethylformamide (3 mL) was added sodium hydride (8.6 mg, 0.22 mmol, 60% in oil) under nitrogen atmosphere or an ice bath (0° C.). Following 30 minutes of stirring at room temperature, 2-(4-chloromethyl-benzyloxy)-pyridine (43.4 mg, 0.19 mmol) described in Manufacturing Example 30-1-1 was added and stirred for 30 minutes at 60° C. The reaction mixture was partitioned into water and ethyl acetate 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, then ethyl acetate only) to obtain the tile compound (22.8 mg, 43%).

Workup

  1. custom(0° C.)
  2. additionwas added
  3. stirringstirred for 30 minutes at 60° C
  4. customThe reaction mixture was partitioned into water and ethyl acetate at room temperature
  5. washThe organic layer was washed with water and saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under a reduced pressure
  8. customThe residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-602ba30cc7e44b259b54d82590002f7a
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

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