Thiophenol → HCID 59469037, compound

HRID 605773Notes

Reaction equation

HRID 605773 reaction equation
[F:1][C:2]1[C:3]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([I:41])=[CH:37][C:36]=2[F:42])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([CH:16]3[CH2:21][N:20](S(C4C=CC=CC=4[N+]([O-])=O)(=O)=O)[CH2:19][CH2:18][NH:17]3)([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].C(=O)([O-])[O-].[K+].[K+].C1(S)C=CC=CC=1>CN(C=O)C>[F:1][C:2]1[C:3]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([I:41])=[CH:37][C:36]=2[F:42])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([CH:16]3[CH2:21][NH:20][CH2:19][CH2:18][NH:17]3)([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 67051877HCID 67051877, compound

Product 1

HCID 59469037HCID 59469037, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{4-[(2-nitrophenyl)sulfonyl]piperazin-2-yl}azetidin-3-ol (139.4 mg, 0.19 mmol) in DMF (1 mL) was added potassium carbonate (79 mg, 0.57 mmol) and thiophenol (21 μL, 0.21 mmol). The mixture was stirred for 45 min at room temperature then quenched with water. The aqueous mixture was extracted twice with ethyl acetate, and the combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by preparative reverse phase HPLC to provide 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-piperazin-2-ylazetidin-3-ol as a white solid (26.8 mg, 0.05 mmol). 1H NMR (400 MHz, CD3OD): 7.45 (dd, 1H), 7.36 (m, 1H), 7.32 (m, 1H), 7.03 (m, 1H), 6.62 (ddd, 1H), 4.51 (br dd, 1H), 4.31 (br dd, 1H), 4.17-3.92 (m, 4H), 3.73-3.56 (m, 3H), 3.46 (br m, 1H), 3.26 (m, 1H); MS (EI) for C20H20F3IN4O2: 533 (MH+).

Workup

  1. customthen quenched with water
  2. extractionThe aqueous mixture was extracted twice with ethyl acetate
  3. dry with materialthe combined organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-ff774d3ac76348e18fa8f11f0f85e67f
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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