Water → 3-(3-(4-(6-Methyl-pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 77835Notes

Reaction equation

HRID 77835 reaction equation
[C:1]([C:3]1[C:4]([NH2:10])=[N:5][C:6]([NH2:9])=[CH:7][CH:8]=1)#[CH:2].[CH3:11][C:12]1[N:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27](Cl)=[N:28][OH:29])=[CH:22][CH:21]=2)[CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.O>O1CCCC1.C(OCC)(=O)C>[CH3:11][C:12]1[N:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]3[CH:2]=[C:1]([C:3]4[C:4]([NH2:10])=[N:5][C:6]([NH2:9])=[CH:7][CH:8]=4)[O:29][N:28]=3)=[CH:22][CH:21]=2)[CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 552816763-Ethynylpyridine-2,6-diamineHCID 72262881(4-(6-Methyl-pyridin-2-yloxymethyl)-phenyl)-acetohydroximoyl chloride

Product 1

HCID 441596003-(3-(4-(6-Methyl-pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 73.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-ethynyl-pyridin-2,6-diamine (300 mg, 2.25 mmol) described in Manufacturing Example 13-1-3 in anhydrous tetrahydrofuran (30 mL) was added (4-(6-methyl-pyridin-2-yloxymethyl)-phenyl)-acetohydroximoyl chloride (1.50 g, 5.16 mmol) described in Manufacturing Example 3-1-5 under nitrogen atmosphere at room temperature. Triethylamine (1.25 mL, 9.00 mmol) was then added dropwise at room temperature, and stirred for 1.5 hours at room temperature. Water and ethyl acetate were added to the reaction mixture at room temperature, and the organic layer was separated. 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) to obtain the title compound (637 mg, 73%).

Workup

  1. customdescribed in Manufacturing Example 3-1-5 under nitrogen atmosphere at room temperature
  2. customthe organic layer was separated
  3. washThe organic layer was washed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under a reduced pressure
  6. customThe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=2:1)

Sources & evidence

ORD record
ord-96d592cdfbad4b9499cc21e4d100e4b5
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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