C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine → 3-[2-Hydroxy-3-(1-hydroxyethyl)phenylamino]-4-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dione

HRID 1528163Notes

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:18](=[O:33])[C:19](=O)[C:20]=1[NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]([OH:30])[CH3:29])[C:23]=1[OH:31])C>CO>[OH:31][C:23]1[C:24]([CH:28]([OH:30])[CH3:29])=[CH:25][CH:26]=[CH:27][C:22]=1[NH:21][C:20]1[C:17](=[O:16])[C:18](=[O:33])[C:19]=1[NH:13][CH:7]([C:5]1[O:6][C:2]([CH3:1])=[CH:3][CH:4]=1)[C:8]1([CH3:12])[CH2:9][O:10][CH2:11]1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 314 mg (1.73 mmol, 1.2 eq) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine and 400 g (1.44 mmol, 1 eq) of 3-ethoxy-4-[2-hydroxy-3-(1-hydroxyethyl)phenylamino]cyclobut-3-ene-1,2-dione in 15 ml of methanol was heated at 50° C. for 2 days. The reaction medium was evaporated and the residue was chromatographed on silica gel HP (column RediSep Rf Gold 40 g, Spot II) eluted with dichloromethane/methanol (gradient). The amorphous solid was taken up with a little diethyl ether, filtered and dried under vacuum at 50° C. 151 mg of 3-[2-hydroxy-3-(1-hydroxyethyl)phenylamino]-4-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dione were obtained in the form of an orange solid. (Mp=129-131° C.). Yield=25%. LC/MS: 96.1% [412]: 2 diastereoisomers.

Workup

customThe reaction medium was evaporated
customthe residue was chromatographed on silica gel HP (column RediSep Rf Gold 40 g, Spot II)
washeluted with dichloromethane/methanol (gradient)
filtrationfiltered
customdried under vacuum at 50° C

Sources & evidence

ORD record: ord-5a4438e3bf404baabdd65880f7de0e4f
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090596B2

Reaction notes

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