Triethylamine → 3-(3-(4-(6-Methyl-pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

HRID 77803Notes

Reaction equation

HRID 77803 reaction equation
[C:1]([C:3]1[C:4]([NH2:9])=[N:5][CH:6]=[CH:7][CH:8]=1)#[CH:2].[CH3:10][C:11]1[N:16]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][C:26](Cl)=[N:27][OH:28])=[CH:21][CH:20]=2)[CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C>O1CCCC1>[CH3:10][C:11]1[N:16]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][C:26]3[CH:2]=[C:1]([C:3]4[C:4]([NH2:9])=[N:5][CH:6]=[CH:7][CH:8]=4)[O:28][N:27]=3)=[CH:21][CH:20]=2)[CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 124225263-Ethynylpyridin-2-amineHCID 72262881(4-(6-Methyl-pyridin-2-yloxymethyl)-phenyl)-acetohydroximoyl chloride

Product 1

HCID 167190503-(3-(4-(6-Methyl-pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamineYield 11.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-ethynyl-pyridin-2-ylamine (30 mg, 0.25 mmol) described in Manufacturing Example 1-2-3 in anhydrous tetrahydrofuran (5 mL) was added (4-(6-methyl-pyridin-2-yloxymethyl)-phenyl)-acetohydroximoyl chloride (222 mg, 0.76 mmol) described in Manufacturing Example 3-1-5 at room temperature. Triethylamine (142 μL, 1.0 mmol) was added dropwise to the reaction solution, and stirred overnight at room temperature. The reaction mixture was partitioned into water and ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3 then 1:1) to obtain the title compound (10.5 mg, 11%).

Workup

  1. customdescribed in Manufacturing Example 3-1-5 at room temperature
  2. customThe reaction mixture was partitioned into water and ethyl acetate
  3. washThe organic layer was washed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under a reduced pressure
  6. customThe residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-61c4ffae22ba4c2c93dc03e1a370fc07
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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