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

HRID 1528175Notes

Reaction equation

HRID 1528175 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.[OH:14][C:15]1[C:20]([C:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[O:22])=[CH:19][CH:18]=[CH:17][C:16]=1[NH:29][C:30]1[C:31](=O)[C:32](=[O:36])[C:33]=1[O:34]C>CO>[OH:14][C:15]1[C:20]([C:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[O:22])=[CH:19][CH:18]=[CH:17][C:16]=1[NH:29][C:30]1[C:33](=[O:34])[C:32](=[O:36])[C:31]=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

4

Reactant 2

HCID 89525357C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamineHCID 895263243-[2-Hydroxy-3-(morpholine-4-carbonyl)phenylamino]-4-methoxycyclobut-3-ene-1,2-dione

Product 1

HCID 715253453-[2-Hydroxy-3-(morpholine-4-carbonyl)phenylamino]-4-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dioneYield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

205 mg (1.13 mmol) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine in solution in 3 ml of methanol were added to a suspension of 249 mg (0.75 mmol) of 3-[2-hydroxy-3-(morpholine-4-carbonyl)phenylamino]-4-methoxycyclobut-3-ene-1,2-dione in 22 ml of methanol. The reaction medium was then heated at 50° C. for two hours and stirred at ambient temperature for 3 days. The reaction medium was concentrated. The residue was taken up with ethyl acetate and was washed twice with a 1 M aqueous sodium dihydrogen phosphate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel (25 g prepacked column: eluent heptane/ethyl acetate from 80% to 100% of ethyl acetate). 0.23 g of product were obtained in the form of a yellow solid. Yield=64%, HPLC purity=98.01%

Workup

  1. concentrationThe reaction medium was concentrated
  2. washwas washed twice with a 1 M aqueous sodium dihydrogen phosphate solution
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel (25 g prepacked column: eluent heptane/ethyl acetate from 80% to 100% of ethyl acetate)

Sources & evidence

ORD record
ord-a0890e4790b24ffeae83002663a44925
Source dataset
uspto-grants-2015_07
Patent number
US09090596B2

Reaction notes

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