Tetrahydrofuran → 3-(3-(3-Pyridin-2-yl-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 640426Notes

Reaction equation

HRID 640426 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[C:9]([CH2:13][C:14](Cl)=[N:15][OH:16])[CH:10]=[CH:11][CH:12]=1.O1CCCC1.[C:23]([C:25]1[C:26]([NH2:32])=[N:27][C:28]([NH2:31])=[CH:29][CH:30]=1)#[CH:24].C(N(CC)CC)C>O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[C:9]([CH:10]=[CH:11][CH:12]=1)[CH2:13][C:14]1[CH:24]=[C:23]([C:25]2[C:26]([NH2:32])=[N:27][C:28]([NH2:31])=[CH:29][CH:30]=2)[O:16][N:15]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 552816763-Ethynylpyridine-2,6-diamineHCID 72262900HCID 72262900, compound

Product 1

HCID 592553873-(3-(3-Pyridin-2-yl-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of (3-(pyridin-2-yl)-phenyl)-acetohydroximoyl chloride (50 mg) described in Manufacturing Example 84-1-3 and tetrahydrofuran (2 mL) were added 3-ethynyl-pyridin-2,6-diamine (6.0 mg, 0.045 mmol) described in Manufacturing Example 13-1-3 and triethylamine (38 μL, 0.27 mmol), which was stirred for 2 hours at room temperature. Water was added to the reaction mixture at the same temperature, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate) to obtain the title compound in a crude product. Then, the residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (3.7 mg, 14%) as a ditrifluoroacetic acid salt.

Workup

  1. extractionwas extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium chloride
  3. concentrationwas concentrated under a reduced pressure
  4. customThe residue was purified by NH silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-2e12c992952e4d1e97ddb2481e27450d
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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