1,2-Dichloroethane → N-(5-Methyl-4-isoxazolyl)-2-[(phenylmethyl)oxy]-5-(4-pyridinyl)benzamide

HRID 1623803Notes

Reaction equation

HRID 1623803 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[CH:14][C:10]=2[C:11]([OH:13])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)CCl.[CH:28]1C=C[C:31]2[N:36]([OH:37])N=[N:34][C:32]=2[CH:33]=1.CC1ON=CC=1N>CN(C)C=O.O>[CH3:28][C:33]1[O:37][N:36]=[CH:31][C:32]=1[NH:34][C:11](=[O:13])[C:10]1[CH:14]=[C:15]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[CH:16]=[CH:17][C:9]=1[O:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 130332025-Methyl-1,2-oxazol-4-amineHCID 669904822-(Benzyloxy)-5-(pyridin-4-yl)benzoic acid

Product 1

HCID 68108126N-(5-Methyl-4-isoxazolyl)-2-[(phenylmethyl)oxy]-5-(4-pyridinyl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-[(phenylmethyl)oxy]-5-(4-pyridinyl)benzoic acid (may be prepared as described in Description 79; 100 mg, 0.30 mmol), EDC (115 mg, 0.60 mmol), and HOBT (92 mg, 0.60 mmol) in dimethylformamide (2 ml) was stirred in air at room temperature for 1 h, then 5-methyl-4-isoxazolamine (may be prepared as described in Description 93; 100 mg, 1.02 mmol) was added in one charge. The reaction mixture was stirred at 25° C. overnight. The solution was heated at 35° C. for 7 hours, then diluted with water (30 ml) and extracted with ethyl acetate (80 ml×3). The organic phase was washed with brine (60 ml×2), dried over anhydrous MgSO4, and concentrated. The residue was purified by chromatography (silica gel, 20 g, eluent: dichloromethane/methanol=60:1, 600 ml). The crude product was washed with methanol (2 ml×2), filtered, and dried in vacuum to yield the title compound. 23 mg.

Workup

  1. additioncharge
  2. stirringThe reaction mixture was stirred at 25° C. overnight
  3. temperatureThe solution was heated at 35° C. for 7 hours
  4. extractionextracted with ethyl acetate (80 ml×3)
  5. washThe organic phase was washed with brine (60 ml×2)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (silica gel, 20 g, eluent: dichloromethane/methanol=60:1, 600 ml)
  9. washThe crude product was washed with methanol (2 ml×2)
  10. filtrationfiltered
  11. customdried in vacuum

Sources & evidence

ORD record
ord-5baca243de4b449e9cf995f1838e4ef7
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Reaction notes

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