Triethylamine → 3-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 77831Notes

Reaction equation

HRID 77831 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16](Cl)=[N:17][OH:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([C:22]1[C:23]([NH2:29])=[N:24][C:25]([NH2:28])=[CH:26][CH:27]=1)#[CH:21].C(N(CC)CC)C>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2[CH:21]=[C:20]([C:22]3[C:23]([NH2:29])=[N:24][C:25]([NH2:28])=[CH:26][CH:27]=3)[O:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 552816763-Ethynylpyridine-2,6-diamineHCID 722628734-Benzyloxy-phenyl-acetohydroximoyl chloride

Product 1

HCID 251146023-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-benzyloxy-phenyl-acetohydroximoyl chloride (140 mg, 0.51 mmol) described in Manufacturing Example 1-1-3 and tetrahydrofuran (10 mL) were added 3-ethynyl-pyridin-2,6-diamine (102 mg, 0.76 mmol) described in Manufacturing Example 13-1-3 and triethylamine (0.71 mL, 5.1 mmol), which was stirred overnight at room temperature. The reaction mixture was then stirred for further 1.5 hours at 55° C. The reaction solution was cooled to room temperature and concentrated under a reduced pressure. The residue was filtered by NH silica gel column chromatography (ethyl acetate) to obtain a crude product. The crude product was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid). The solvent was evaporated under a reduced pressure, and the residue was filtered with NH silica gel to obtain the title compound (51 mg, 27%).

Workup

  1. stirringThe reaction mixture was then stirred for further 1.5 hours at 55° C
  2. temperatureThe reaction solution was cooled to room temperature
  3. concentrationconcentrated under a reduced pressure
  4. filtrationThe residue was filtered by NH silica gel column chromatography (ethyl acetate)
  5. customto obtain a crude product
  6. customThe crude product was purified by reverse-phase high performance liquid chromatography (
  7. additioncontaining 0.1% trifluoroacetic acid)
  8. customThe solvent was evaporated under a reduced pressure
  9. filtrationthe residue was filtered with NH silica gel

Sources & evidence

ORD record
ord-c155553956484b808e8964f4897bd515
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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