4-Methylmorpholine → 5-((E)-2-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}ethenyl)-3-propyl-1,2,4-oxadiazole

HRID 2221830Notes

Reaction equation

HRID 2221830 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:39])=[C:9]([CH2:11][O:12][C:13]2[CH:36]=[CH:35][C:16]([CH2:17][O:18][C:19]3[C:23](/[CH:24]=[CH:25]/[C:26](O)=[O:27])=[CH:22][N:21]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:20]=3)=[CH:15][C:14]=2[O:37][CH3:38])[N:10]=1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.O[N:71]=[C:72]([NH2:76])[CH2:73][CH2:74][CH3:75]>O.CN(C)C=O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:39])=[C:9]([CH2:11][O:12][C:13]2[CH:36]=[CH:35][C:16]([CH2:17][O:18][C:19]3[C:23](/[CH:24]=[CH:25]/[C:26]4[O:27][N:76]=[C:72]([CH2:73][CH2:74][CH3:75])[N:71]=4)=[CH:22][N:21]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:20]=3)=[CH:15][C:14]=2[O:37][CH3:38])[N:10]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2794811N-HydroxybutyramidineHCID 27960291-Hydroxybenzotriazole hydrateHCID 69215034(2E)-3-{3-[(4-([2-(2-furyl)-5-methyl-4-oxazolyl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}-2-propenoic acid

Product 1

HCID 692175215-((E)-2-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}ethenyl)-3-propyl-1,2,4-oxadiazoleYield 18%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (2E)-3-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}-2-propenoic acid (0.60 g), 4-methylmorpholine (0.28 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.21 g), 1-hydroxybenzotriazole monohydrate (0.17 g) and N,N-dimethylformamide (30 mL) was stirred at room temperature for 30 min, N′-hydroxybutanimidamide (0.14 g) was added, and the mixture was further stirred at room temperature for 15 hrs. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. Xylene (50 mL) was added to the residue, and the mixture was heated under reflux for 24 hrs. The reaction mixture was concentrated, and the obtained residue was subjected to silica gel column chromatography to give 5-((E)-2-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}ethenyl)-3-propyl-1,2,4-oxadiazole as colorless crystals (0.12 g, yield 18%) from a fraction eluted with ethyl acetate-hexane (1:2, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 192-193° C.

Workup

  1. stirringthe mixture was further stirred at room temperature for 15 hrs
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. additionXylene (50 mL) was added to the residue
  7. temperaturethe mixture was heated
  8. temperatureunder reflux for 24 hrs
  9. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-8981891c8c004ce0b1b7cb205773f926
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

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