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

HRID 1436637Notes

Reaction equation

HRID 1436637 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-5205c1e02aad472c889fddeb9f430e2c
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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