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

HRID 77878

Reaction equation

HRID 77878 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 on 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 title compound (22.8 mg, 43%).

Workup

  1. additionwas added
  2. stirringstirred for 30 minutes at 60° C
  3. customThe reaction mixture was partitioned into water and ethyl acetate 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

Sources & evidence

ORD record
ord-804b157de554464e85ebe53b2a9c687b
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Linked notes

Loading…