Tetrahydrofuran → N-Methyl-5-(3-methyl-[1,2,4]oxadiazol-5-yl)-N-propyl-isophthalamic acid ethyl ester

HRID 732494Notes

Reaction equation

HRID 732494 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:13]=[C:12]([C:14](=[O:20])[N:15]([CH3:19])[CH2:16][CH2:17][CH3:18])[CH:11]=[C:7]([C:8]([OH:10])=O)[CH:6]=1)[CH3:2].Cl.CN(C)CCCN=C=[N:30][CH2:31][CH3:32].C1COCC1.[F-].C([N+:44](CCCC)(CCCC)CCCC)CCC>ClCCl>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:6]=[C:7]([C:8]2[O:10][N:44]=[C:31]([CH3:32])[N:30]=2)[CH:11]=[C:12]([C:14]([N:15]([CH3:19])[CH2:16][CH2:17][CH3:18])=[O:20])[CH:13]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724141Tetrabutylammonium FluorideHCID 688146805-(Methyl-propylcarbamoyl)-isophthalic acid monoethyl ester

Product 1

HCID 68815853N-Methyl-5-(3-methyl-[1,2,4]oxadiazol-5-yl)-N-propyl-isophthalamic acid ethyl esterYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Stir a solution of 5-(methyl-propyl-carbamoyl)-isophthalic acid monoethyl ester (330 mg, 1.13 mmol), acetamideoxime (117 mg, 1.58 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (303 mg, 1.58 mmol) in dichloromethane (20 mL) at room temperature overnight. Concentrate and purify (silica gel chromatography, eluting with 2:98 methanol:dichloromethane). Concentrate and add THF (30 mL) and 1 N tetrabutylammonium fluoride in THF (43 μL, 0.043 mmol). Reflux the solution for 30 min and concentrate. Add ethyl acetate, extract with saturated aqueous sodium chloride, dry (magnesium sulfate) concentrate and purify (silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes) to give the title compound (135 mg, 36%).

Workup

  1. concentrationConcentrate
  2. custompurify
  3. wash(silica gel chromatography, eluting with 2:98 methanol:dichloromethane)
  4. concentrationConcentrate
  5. temperatureReflux the solution for 30 min
  6. concentrationconcentrate
  7. extractionAdd ethyl acetate, extract with saturated aqueous sodium chloride
  8. dry with materialdry (magnesium sulfate)
  9. concentrationconcentrate
  10. custompurify
  11. wash(silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-014e43d201ac4a7d825339188a1a4312
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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