Trifluoroacetic acid → 4-(5-(6-Amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol

HRID 640468Notes

Reaction equation

HRID 640468 reaction equation
FC(F)(F)C(O)=O.C([O:15][C:16]1[CH:34]=[CH:33][C:19]([CH2:20][C:21]2[CH:25]=[C:24]([C:26]3[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=3)[O:23][N:22]=2)=[CH:18][CH:17]=1)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>O>[NH2:32][C:29]1[N:30]=[CH:31][C:26]([C:24]2[O:23][N:22]=[C:21]([CH2:20][C:19]3[CH:33]=[CH:34][C:16]([OH:15])=[CH:17][CH:18]=3)[CH:25]=2)=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7520ThioanisoleHCID 516892Sodium BicarbonateHCID 592554535-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

Product 1

HCID 592554134-(5-(6-Amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenolYield 74.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a trifluoroacetic acid (5 mL) solution of 5-(3-(4-benzyloxy-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine (270 mg, 0.755 mmol) described in Example 28 was added thioanisole (355 μL, 3.02 mmol) at 0° C., which was stirred for 1 hour and 20 minutes at room temperature. Sodium hydrogencarbonate and water were added to the reaction mixture at 0° C., which was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1) to obtain the title compound (150 mg, 74%).

Workup

  1. extractionwhich was extracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under a reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1)

Sources & evidence

ORD record
ord-8aed46ce38d44716abff4b90ad0cf1bf
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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