Tetrahydrofuran → 3-(3-(6-(2-Fluorophenoxy)-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 78127Notes

Reaction equation

HRID 78127 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[O:4][C:5]1[N:10]=[CH:9][C:8]([CH2:11][C:12](Cl)=[N:13][OH:14])=[CH:7][CH:6]=1.O1CCCC1.[C:25]([C:27]1[C:28]([NH2:34])=[N:29][C:30]([NH2:33])=[CH:31][CH:32]=1)#[CH:26].C(N(CC)CC)C>O>[F:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[O:4][C:5]1[N:10]=[CH:9][C:8]([CH2:11][C:12]2[CH:26]=[C:25]([C:27]3[C:28]([NH2:34])=[N:29][C:30]([NH2:33])=[CH:31][CH:32]=3)[O:14][N:13]=2)=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 552816763-Ethynylpyridine-2,6-diamineHCID 72262887(6-(2-Fluoro-phenoxy)-pyridin-3-yl)-acetohydroximoyl chloride

Product 1

HCID 592552143-(3-(6-(2-Fluorophenoxy)-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 45.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of (6-(2-fluoro-phenoxy)-pyridin-3-yl)-acetohydroximoyl chloride (28 mg) described in Manufacturing Example 74-1-4 and tetrahydrofuran (1 mL) were added 3-ethynyl-pyridin-2,6-diamine (10 mg, 0.075 mmol) described in Manufacturing Example 13-1-3 and triethylamine (21 μL, 0.15 mmol), which was stirred for 5 hours at room temperature. Water was added to the reaction mixture at the same temperature, which 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 alone) to obtain the title compound (13 mg, 45%).

Workup

  1. extractionwas extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium chloride
  3. concentrationwas concentrated under a reduced pressure
  4. customThe residue was purified by NH silica gel column chromatography (ethyl acetate alone)

Sources & evidence

ORD record
ord-18871a94bb814e10bf4d87ffa6d6e0de
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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