Tetrahydrofuran → HCID 59255358, compound

HRID 640325Notes

Reaction equation

HRID 640325 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[C:9]([CH2:13][C:14](Cl)=[N:15][OH:16])[CH:10]=[CH:11][CH:12]=1.O1CCCC1.[C:23]([C:25]1[C:26]([NH2:31])=[N:27][CH:28]=[CH:29][CH:30]=1)#[CH:24].C(N(CC)CC)C>O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[C:9]([CH:10]=[CH:11][CH:12]=1)[CH2:13][C:14]1[CH:24]=[C:23]([C:25]2[C:26]([NH2:31])=[N:27][CH:28]=[CH:29][CH:30]=2)[O:16][N:15]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 124225263-Ethynylpyridin-2-amineHCID 72262900HCID 72262900, compound

Product 1

HCID 59255358HCID 59255358, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of (3-(pyridin-2-yl)-phenyl)-acetohydroximoyl chloride (100 mg) described in Manufacturing Example 84-1-3 and tetrahydrofuran (2 mL) were added 3-ethynyl-pyridin-2-ylamine (10 mg, 0.20 mmol) described in Manufacturing Example 1-2-3 and triethylamine (71 μL, 0.51 mmol) at room temperature, which was stirred for 2.5 hours at 55° C. The reaction 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) to obtain the title compound (7.2 mg, 15%) as a ditrifluoracetic acid salt.

Workup

  1. temperatureThe reaction 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-7c6d37836c30477cb98a89848c4d4a81
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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