Tetrahydrofuran → 3-(3-(3-Fluoro-4-(5-fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)pyridin-2-ylamine

HRID 1891786Notes

Reaction equation

HRID 1891786 reaction equation
O1CCCC1.[F:6][C:7]1[CH:8]=[C:9]([CH2:22][C:23](Cl)=[N:24][OH:25])[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1.[C:27]([C:29]1[C:30]([NH2:35])=[N:31][CH:32]=[CH:33][CH:34]=1)#[CH:28]>O>[F:6][C:7]1[CH:8]=[C:9]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1)[CH2:22][C:23]1[CH:28]=[C:27]([C:29]2[C:30]([NH2:35])=[N:31][CH:32]=[CH:33][CH:34]=2)[O:25][N:24]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 124225263-Ethynylpyridin-2-amineHCID 72262901(3-Fluoro4-(5-fluoro-pyridin-2-ylmethoxy)-phenyl)-acetohydroximoyl chloride

Product 1

HCID 592554113-(3-(3-Fluoro-4-(5-fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)pyridin-2-ylamineYield 13.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a tetrahydrofuran (5.00 mL) solution of (3-fluoro-4-(5-fluoro-pyridin-2-ylmethoxy)-phenyl)-acetohydroximoyl chloride (170 mg, 0.554 mmol) described in Manufacturing Example 94-1-3 and 3-ethynyl-pyridin-2-ylamine (40.0 mg, 0.339 mmol) described in Manufacturing Example 1-2-3 was added tiethylamine (142 μL, 1.02 mmol) at room temperature, which was stirred for 4 hours at room temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was washed with 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=1:3→1:2) to obtain the title compound (18.0 mg, 13.5%).

Workup

  1. additionwas added tiethylamine (142 μL, 1.02 mmol) at room temperature
  2. extractionwhich was then extracted with ethyl acetate
  3. washThe organic layer was washed with 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=1:3→1:2)

Sources & evidence

ORD record
ord-d6c3b7a0387f4261a88e04d02f7705e7
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

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