3-((2-Ethoxy-3,4-dioxocyclobut-1-en-1-yl)amino)-2-hydroxy-N,N-dimethylbenzamide → 3-(4-Hydroxy-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-5-ylamino)-4-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dione

HRID 1528172Notes

Reaction equation

HRID 1528172 reaction equation
[CH3:1][C:2]1[O:6][C:5]([CH:7]([NH2:13])[C:8]2([CH3:12])[CH2:11][O:10][CH2:9]2)=[CH:4][CH:3]=1.C([O:16][C:17]1[C:20](=[O:21])[C:19](=O)[C:18]=1[NH:23][C:24]1[C:25]([OH:35])=[C:26]([CH:32]=[CH:33][CH:34]=1)[C:27]([N:29]([CH3:31])[CH3:30])=[O:28])C>CO>[OH:35][C:25]1[C:24]([NH:23][C:18]2[C:17](=[O:16])[C:20](=[O:21])[C:19]=2[NH:13][CH:7]([C:5]2[O:6][C:2]([CH3:1])=[CH:3][CH:4]=2)[C:8]2([CH3:12])[CH2:9][O:10][CH2:11]2)=[CH:34][CH:33]=[C:32]2[C:26]=1[C:27](=[O:28])[N:29]([CH3:31])[CH2:30]2

Participants

4

Reactant 2

HCID 118554143-((2-Ethoxy-3,4-dioxocyclobut-1-en-1-yl)amino)-2-hydroxy-N,N-dimethylbenzamideHCID 89525357C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine

Product 1

HCID 715253433-(4-Hydroxy-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-5-ylamino)-4-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dioneYield 4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
55 °C

Procedure

287 mg (1.58 mmol) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine in 3 ml of methanol were added to a suspension of 235 mg (0.78 mmol) of 3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N,N-dimethylbenzamide in 20 ml of methanol at 55° C. The reaction medium was heated at 55° C. for 24 hours and then concentrated to dryness. The residue was chromatographed on silica gel (40 g prepacked column, 30 ml/min, 100% dichloromethane then 4% of methanol). A residue of 130 mg was obtained and was purified by preparative TLC (eluent: 50/50/1 ethyl acetate/acetone/water). 52 mg were obtained and then precipitated from dimethyl sulfoxide and filtered off 15 mg of product were obtained in the form of a white solid. Yield=4%, HPLC=98.56%

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was chromatographed on silica gel (40 g prepacked column, 30 ml/min, 100% dichloromethane
  3. customA residue of 130 mg was obtained
  4. customwas purified by preparative TLC (eluent: 50/50/1 ethyl acetate/acetone/water)
  5. custom52 mg were obtained
  6. customprecipitated from dimethyl sulfoxide
  7. filtrationfiltered off 15 mg of product
  8. customwere obtained in the form of a white solid

Sources & evidence

ORD record
ord-4c92c1d3a706425b83797618d612042e
Source dataset
uspto-grants-2015_07
Patent number
US09090596B2

Reaction notes

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