3-[4-Chloro-2-hydroxy-3-(4-methylpiperazine-1-sulfonyl)phenylamino]-4-ethoxycyclobut-3-ene-1,2-dione → 3-[4-chloro-2-hydroxy-3-(4-methylpiperazine-1-sulfonyl)phenylamino]-4-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dione

HRID 1528221Notes

Reaction equation

HRID 1528221 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C@H:7]([NH2:13])[C:8]2([CH3:12])[CH2:11][O:10][CH2:9]2)=[CH:4][CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]2[C:23](=O)[C:24](=[O:29])[C:25]=2[O:26]CC)=[C:17]([OH:31])[C:16]=1[S:32]([N:35]1[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]1)(=[O:34])=[O:33]>CO>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]2[C:25](=[O:26])[C:24](=[O:29])[C:23]=2[NH:13][C@@H: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)=[C:17]([OH:31])[C:16]=1[S:32]([N:35]1[CH2:36][CH2:37][N:38]([CH3:41])[CH2:39][CH2:40]1)(=[O:33])=[O:34]

Participants

4

Reactant 2

HCID 895254983-[4-Chloro-2-hydroxy-3-(4-methylpiperazine-1-sulfonyl)phenylamino]-4-ethoxycyclobut-3-ene-1,2-dioneHCID 89525580C-(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine

Product 1

HCID 715553613-[4-chloro-2-hydroxy-3-(4-methylpiperazine-1-sulfonyl)phenylamino]-4-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dioneYield 68.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 250 mg (1.4 mmol, 1.2 eq) of C—(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine (prepared in EXAMPLE 50, steps 1 to 4) and 500 mg (1.16 mmol, 1 eq) of 3-[4-chloro-2-hydroxy-3-(4-methylpiperazine-1-sulfonyl)phenylamino]-4-ethoxycyclobut-3-ene-1,2-dione in 20 ml of methanol was heated at 50° C. for 16 hours. The methanol was evaporated off and the residue was chromatographed on silica gel eluted with dichloromethane/methanol (98/2). The residue was washed with a 1 M aqueous sodium dihydrogen phosphate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and evaporated. 450 mg of 3-[4-chloro-2-hydroxy-3-(4-methylpiperazine-1-sulfonyl)phenylamino]-4-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dione were obtained in the form of a dark yellow solid. Yield=68%.

Workup

  1. customThe methanol was evaporated off
  2. customthe residue was chromatographed on silica gel
  3. washeluted with dichloromethane/methanol (98/2)
  4. washThe residue was washed with a 1 M aqueous sodium dihydrogen phosphate solution
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-f8c9f4e762184bc0b6385acaf8cdeb15
Source dataset
uspto-grants-2015_07
Patent number
US09090596B2

Reaction notes

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