Tetrahydrofuran → 3-(3-(4-(4-Methyl-pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

HRID 640178Notes

Reaction equation

HRID 640178 reaction equation
O1CCCC1.[CH3:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22](Cl)=[N:23][OH:24])=[CH:17][CH:16]=2)[CH:8]=1.[C:26]([C:28]1[C:29]([NH2:34])=[N:30][CH:31]=[CH:32][CH:33]=1)#[CH:27].C(N(CC)CC)C>O>[CH3:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]3[CH:27]=[C:26]([C:28]4[C:29]([NH2:34])=[N:30][CH:31]=[CH:32][CH:33]=4)[O:24][N:23]=3)=[CH:17][CH:16]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 124225263-Ethynylpyridin-2-amineHCID 72262895(4-(4-Methyl-pyridin-2-yloxymethyl)phenyl)-acetohydroximoyl chloride

Product 1

HCID 592552823-(3-(4-(4-Methyl-pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 22.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a tetrahydrofuran (7.00 mL) solution of (4-(4-methyl-pyridin-2-yloxymethyl)-phenyl)-acetohydroximoyl chloride (270 mg, 0.930 mmol) described in Manufacturing Example 43-1-5 and 3-ethynyl-pyridin-2-ylamine (40.0 mg, 0.339 mmol) described in Manufacturing Example 1-2-3 was added triethylamine (189 μL, 1.36 mmol) at room temperature, which was stirred at room temperature for 4 hours. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3→1:2) to obtain the title compound (28.9 mg, 20.6%).

Workup

  1. extractionwhich was then extracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customThe filtrate was evaporated under a reduced pressure
  7. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3→1:2)

Sources & evidence

ORD record
ord-934d94e06cda4e69bca0f9e52a8356ab
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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