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

HRID 640285Notes

Reaction equation

HRID 640285 reaction equation
O1CCCC1.[C:6]([C:8]1[C:9]([NH2:14])=[N:10][CH:11]=[CH:12][CH:13]=1)#[CH:7].[F:15][C:16]1[CH:33]=[CH:32][CH:31]=[CH:30][C:17]=1[O:18][C:19]1[N:24]=[CH:23][C:22]([CH2:25][C:26](Cl)=[N:27][OH:28])=[CH:21][CH:20]=1.C(N(CC)CC)C>O>[F:15][C:16]1[CH:33]=[CH:32][CH:31]=[CH:30][C:17]=1[O:18][C:19]1[N:24]=[CH:23][C:22]([CH2:25][C:26]2[CH:7]=[C:6]([C:8]3[C:9]([NH2:14])=[N:10][CH:11]=[CH:12][CH:13]=3)[O:28][N:27]=2)=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 124225263-Ethynylpyridin-2-amineHCID 72262887(6-(2-Fluoro-phenoxy)-pyridin-3-yl)-acetohydroximoyl chloride

Product 1

HCID 592551803-(3-(6-(2-Fluoro-phenoxy)-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2-ylamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

To a tetrahydrofuran (1 mL) solution of 3-ethynyl-pyridin-2-ylamine (9.0 mg, 0.076 mmol) described in Manufacturing Example 1-2-3 and (6-(2-fluoro-phenoxy)-pyridine-3-yl)-acetohydroximoyl chloride (28 mg) described in Manufacturing Example 74-1-4 was added triethylamine (21 μL, 0.15 mmol), which was stirred for 5 hours at 55° C. The mixture was cooled to room temperature and water was added at that temperature, followed by extraction 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:heptane=2:1) to obtain the title compound as a crude product. This was then purified by reverse-phase high-performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoracetic acid). Triethylamine was added to make the solvent basic when concentrating the mobile phase, and the eluate was concentrated under a reduced pressure. The resulting residue was washed with water to obtain the title compound (1.0 mg, 4%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. concentrationwas concentrated under a reduced pressure
  5. customThe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=2:1)

Sources & evidence

ORD record
ord-3ed0c10444c4455e8f642a8224575fb5
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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