3-(2-Ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxybenzoic acid → 2-Hydroxy-3-(2-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzoic acid

HRID 1528155Notes

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:33])=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([OH:29])=[O:28])C>CO>[OH:33][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:32][CH:31]=[CH:30][C:26]=1[C:27]([OH:29])=[O:28]

Participants

Conditions

Temperature: 50 °C

Procedure

453 mg (2.5 mmol, 1.5 eq) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine were added to 471 mg (1.7 mmol, 1 eq) of 3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxybenzoic acid dissolved under hot conditions in 50 ml of methanol. The reaction medium was heated at 50° C. for 18 hours and then at 60° C. for 7 days. The methanol was evaporated off and the residue was chromatographed on silica gel (column puriFlash IR50SI-120G, Spot II) eluted with dichloromethane/methanol (gradient). The solid was taken up with a little ethyl acetate, filtered and dried under vacuum at 55° C. 310 mg of 2-hydroxy-3-(2-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzoic acid were obtained in the form of a brown solid. (Mp=180-185° C.). Yield=44%. LC/MS: 97.08% [412].

Workup

customThe methanol was evaporated off
customthe residue was chromatographed on silica gel (column puriFlash IR50SI-120G, Spot II)
washeluted with dichloromethane/methanol (gradient)
filtrationfiltered
customdried under vacuum at 55° C

Sources & evidence

ORD record: ord-58d16cc970a64b6b99bf45dbb23e73d0
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090596B2

Reaction notes

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