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

HRID 1528159Notes

Reaction equation

HRID 1528159 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:38])[C:19](=O)[C:20]=1[NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([N:30]2[CH2:34][CH2:33][C@@H:32]([OH:35])[CH2:31]2)=[O:29])[C:23]=1[OH:36])C>CO>[OH:36][C:23]1[C:24]([C:28]([N:30]2[CH2:34][CH2:33][C@@H:32]([OH:35])[CH2:31]2)=[O:29])=[CH:25][CH:26]=[CH:27][C:22]=1[NH:21][C:20]1[C:17](=[O:16])[C:18](=[O:38])[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

4

Reactant 2

HCID 89525357C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamineHCID 895263213-ethoxy-4-[2-hydroxy-3-((R)-3-hydroxypyrrolidine-1-carbonyl)phenylamino]cyclobut-3-ene-1,2-dione

Product 1

HCID 715266053-[2-hydroxy-3-((R)-3-hydroxypyrrolidine-1-carbonyl)phenylamino]-4-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dioneYield 72.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

544 mg (3 mmol, 1.5 eq) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine were added to 693 mg (2 mmol, 1 eq) of 3-ethoxy-4-[2-hydroxy-3-((R)-3-hydroxypyrrolidine-1-carbonyl)phenylamino]cyclobut-3-ene-1,2-dione dissolved under hot conditions in 30 ml of methanol. The reaction medium was heated at 50° C. for 3 days and then at 60° C. for 5 hours. The methanol was evaporated off and the residue was chromatographed on silica gel (column puriFlash IR-50SI/80G, Spot II) then subsequently on silica gel (column puriFlash PF-15SIHP/25G×2, Spot II) eluted with dichloromethane/methanol (gradient). 694 mg of 3-[2-hydroxy-3-((R)-3-hydroxypyrrolidine-1-carbonyl)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 amorphous solid. Yield=72%. LC/MS: 99.6% [481].

Workup

  1. customThe methanol was evaporated off
  2. customthe residue was chromatographed on silica gel (column puriFlash IR-50SI/80G, Spot II)
  3. washsubsequently on silica gel (column puriFlash PF-15SIHP/25G×2, Spot II) eluted with dichloromethane/methanol (gradient)

Sources & evidence

ORD record
ord-28047c27d42e4a86850a6e7eb6fb9294
Source dataset
uspto-grants-2015_07
Patent number
US09090596B2

Reaction notes

Loading…