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

HRID 77808Notes

Reaction equation

HRID 77808 reaction equation
[CH2:1]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14](Cl)=[N:15][OH:16])=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH3:4].[C:18]([C:20]1[C:21]([NH2:26])=[N:22][CH:23]=[CH:24][CH:25]=1)#[CH:19].C(N(CC)CC)C>O1CCCC1>[CH2:1]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[CH:19]=[C:18]([C:20]3[C:21]([NH2:26])=[N:22][CH:23]=[CH:24][CH:25]=3)[O:16][N:15]=2)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 124225263-Ethynylpyridin-2-amineHCID 722628614-Butoxymethyl-phenyl-acetohydroximoyl chloride

Product 1

HCID 251141703-(3-(4-Butoxymethyl-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 6.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-butoxymethyl-phenyl-acetohydroximoyl chloride (28 mg, 0.11 mmol) described in Manufacturing Example 4-1-4 and 3-ethynyl-pyridin-2-ylamine (13 mg, 0.11 mmol) described in Manufacturing Example 1-2-3 in tetrahydrofuran (1 mL) was added triethylamine (31 μL, 0.22 mmol) at room temperature, which was stirred for 70 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate at room temperature. 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 (heptane:ethyl acetate=2:1) and then further purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (2.3 mg, 5%) as a trifluoroacetic acid salt.

Workup

  1. customThe reaction solution was partitioned into water and ethyl acetate at room temperature
  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 NH silica gel column chromatography (heptane:ethyl acetate=2:1)
  6. customfurther purified by reverse-phase high performance liquid chromatography (
  7. additioncontaining 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-9636e3545c5a4682a96dc6f8e0340cc1
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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