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

HRID 77863Notes

Reaction equation

HRID 77863 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:30]=[CH:29][C:20]([CH2:21][O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)=[CH:19][CH:18]=1>CN(C)C=O>[N:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[O:22][CH2:21][C:20]1[CH:19]=[CH:18][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:30][CH:29]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 592550952-(4-Chloromethyl-benzyloxy)-pyridineHCID 592552903-(1H-pyrazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 167190843-(1-(4-(Pyridin-2-yloxymethyl)-benzyl)-1H-pyrazol-4-yl)-pyridin-2-ylamineYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1H-pyrazol-4-yl)-pyridin-2-ylamine (150 mg, 0.94 mmol) described in Manufacturing Example 32-1-4 in N,N-dimethylformamide (10 mL) was added sodium hydride (48.7 mg, 1.22 mmol, 60% in oil) on an ice bath (0° C.) under nitrogen atmosphere. Following 40 minutes of stirring at room temperature, 2-(4-chloromethyl-benzyloxy)-pyridine (228 mg, 0.98 mmol) described in Manufacturing Example 30-1-1 was added and stirred for 30 minutes at room temperature. 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) to obtain the title compound (307 mg, 92%).

Workup

  1. additionwas added
  2. stirringstirred for 30 minutes at room temperature
  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-fe9e8d977d5143ab8b3c5d4448ab9875
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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