Tetrahydrofuran → 5-(3-(6-(4-Fluoro-phenoxy)-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2-ylamine

HRID 78193Notes

Reaction equation

[F:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[N:12]=[CH:11][C:10]([CH2:13][C:14](Cl)=[N:15][OH:16])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.O1CCCC1.[C:25]([C:27]1[CH:28]=[CH:29][C:30]([NH2:33])=[N:31][CH:32]=1)#[CH:26].C(N(CC)CC)C>O>[F:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[N:12]=[CH:11][C:10]([CH2:13][C:14]3[CH:26]=[C:25]([C:27]4[CH:28]=[CH:29][C:30]([NH2:33])=[N:31][CH:32]=4)[O:16][N:15]=3)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of (6-(4-fluoro-phenoxy)-pyridin-3-yl)-acetohydroximoyl chloride (25 mg) described in Manufacturing Example 75-1-4 and tetrahydrofuran (1 mL) were added 5-ethynyl-pyridin-2-ylamine (6.0 mg, 0.051 mmol) described in Manufacturing Example 28-1-3 and triethylamine (14 μL, 0.10 mmol), which was stirred for 5 hours at 50° C. The reaction mixture was allowed to room temperature, water was added at the same temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate) to obtain the title compound (3.5 mg, 19%).

Workup

customwas allowed to room temperature
extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with saturated aqueous sodium chloride
concentrationwas concentrated under a reduced pressure
customThe residue was purified by NH silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record: ord-0827f2641d204c8aaaa9e4884fb0e563
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841327B2

Reaction notes

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