Water → N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)acetamide

HRID 2278990Notes

Reaction equation

HRID 2278990 reaction equation
ClN1C(=O)CCC1=O.[CH:9](=[N:11][OH:12])[CH3:10].[C:13]([C:15]1[CH:20]=[C:19]([O:21][C:22]2[CH:23]=[CH:24][C:25]([NH:29][C:30](=[O:32])[CH3:31])=[N:26][C:27]=2[CH3:28])[CH:18]=[CH:17][N:16]=1)#[CH:14].O>CN(C=O)C>[CH3:28][C:27]1[N:26]=[C:25]([NH:29][C:30](=[O:32])[CH3:31])[CH:24]=[CH:23][C:22]=1[O:21][C:19]1[CH:18]=[CH:17][N:16]=[C:15]([C:13]2[O:12][N:11]=[C:9]([CH3:10])[CH:14]=2)[CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7863AldoximeHCID 31398ChlorosuccinimideHCID 90403485N-(5-((2-ethynylpyridin-4-yl)oxy)-6-methylpyridin-2-yl)acetamide

Product 1

HCID 90402502N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)acetamideYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of N-chlorosuccinimide (0.153 g, 1.145 mmol) in DMF (1 mL) was treated with acetaldoxime (0.068 g, 1.145 mmol), stirred at RT for 30 min, then added to a solution of N-(5-((2-ethynylpyridin-4-yl)oxy)-6-methylpyridin-2-yl)acetamide (0.102 g, 0.382 mmol) and TEA (0.5 mL) in DMF (1 mL) and heated at 60° C. for 1 h. The mixture was cooled to RT, treated with H2O, extracted with EtOAc (2×) and the combined organics were washed with H2O, then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)acetamide (110 mg, 89%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.64 (s, 1 H), 8.55 (d, J=5.7 Hz, 1 H), 8.03 (d, J=8.8 Hz, 1 H), 7.64 (d, J=8.8 Hz, 1 H), 7.35 (d, J=2.5 Hz, 1 H), 6.96 (m, 2 H), 2.28 (s, 3 H), 2.25 (s, 3 H), 2.08 (s, 3 H); MS (ESI) m/z: 325.1 (M+H+).

Workup

  1. temperatureheated at 60° C. for 1 h
  2. temperatureThe mixture was cooled to RT
  3. extractionextracted with EtOAc (2×)
  4. washthe combined organics were washed with H2O
  5. dry with materialbrine, dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-91cde338d2b847fb83ed5beb8f033895
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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