Triethylamine → 5-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

HRID 77851Notes

Reaction equation

HRID 77851 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH2:9])=[N:7][CH:8]=1)#[CH:2].[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25](Cl)=[N:26][OH:27])=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C>O1CCCC1>[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]2[CH:2]=[C:1]([C:3]3[CH:4]=[CH:5][C:6]([NH2:9])=[N:7][CH:8]=3)[O:27][N:26]=2)=[CH:20][CH:19]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 219548275-Ethynylpyridin-2-amineHCID 722628734-Benzyloxy-phenyl-acetohydroximoyl chloride

Product 1

HCID 592554535-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 3.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-ethynyl-pyridin-2-ylamine (10 mg, 85 μmol) described in Manufacturing Example 28-1-3 and 4-benzyloxy-phenyl-acetohydroximoyl chloride (70 mg, 0.25 mmol) described in Manufacturing Example 1-1-3 in tetrahydrofuran (2 mL) was added triethylamine (35 μL, 0.25 mmol) at room temperature, which was stirred for 3 hours and 40 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate at 0° C. 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 reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (1 mg, 3%) as a trifluoroacetic acid salt.

Workup

  1. customThe reaction solution was partitioned into water and ethyl acetate at 0° C
  2. washThe organic layer was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under a reduced pressure
  5. customThe residue was purified by reverse-phase high performance liquid chromatography (
  6. additioncontaining 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-086c0ce1b1da4cf3936c1a788c23cadd
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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