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

HRID 78219

Reaction equation

HRID 78219 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:19]=[CH:20][C:21]([O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[N:22][CH:23]=1>CN(C)C=O>[O:24]([C:21]1[N:22]=[CH:23][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:19][CH:20]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 132534765-Chloromethyl-2-phenoxy-pyridineHCID 592551723-(1H-pyrazol-4-yl)-pyridine-2,6-diamine

Product 1

HCID 592553243-(1-(6-Phenoxy-pyridin-3-ylmethyl)-1H-pyrazol-4-yl)-pyridin-2,6-diamineYield 25.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an N,N-dimethylformamide (5.00 mL) solution of 3-(1H-pyrazol-4-yl)-pyridine-2,6-diamine (30.0 mg, 0.171 mmol) described in Manufacturing Example 36-1-2 was added sodium hydride (7.52 mg, 0.188 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 (59.9 mg, 0.273 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) to obtain the title compound (15.4 mg, 25.2%).

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)

Sources & evidence

ORD record
ord-b7753dcec1a24e5bacb72e27b054c634
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Linked notes

Loading…