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

HRID 1693993Notes

Reaction equation

[O:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:6][C:7]1[CH:24]=[CH:23][CH:22]=[CH:21][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16]C(Cl)=NO)=CC=1.C([C:27]1[C:28]([NH2:33])=[N:29][CH:30]=[CH:31][CH:32]=1)#C.[CH2:34]([N:36](CC)CC)C>O>[F:6][C:7]1[CH:24]=[CH:23][CH:22]=[CH:21][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:16][C:2]=1[CH2:3][C:4]1[CH:34]=[N:36][O:1][C:5]=1[C:27]1[C:28]([NH2:33])=[N:29][CH:30]=[CH:31][CH:32]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a tetrahydrofuran (10.0 mL) solution of (4-(2-fluoro-phenoxy)-phenyl)acetohydroximoyl chloride (290 mg, 1.04 mmol) described in Manufacturing Example 83-1-3 and 3-ethynyl-pyridin-2-ylamine (50.0 mg, 0.423 mmol) described in Manufacturing Example 1-2-3 was added triethylamine (177 μL, 1.27 mmol) at room temperature, which was stirred for 30 minutes at 60° C. 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=1:5) to obtain the title compound (57.0 mg, 37.3%).

Workup

extractionwhich was then extracted with ethyl acetate
washThe organic layer was washed with saturated aqueous sodium chloride
dry with materialdried over anhydrous magnesium sulfate
customthe solvent was evaporated under a reduced pressure
customThe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5)

Sources & evidence

ORD record: ord-6f9f471bb9ae45f08008b26b0a622656
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08158657B2

Reaction notes

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