Water → HCID 11704806, compound

HRID 2374098Notes

Reaction equation

HRID 2374098 reaction equation
[F:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][N:7]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][N:26]=[C:25](C(=O)N)[CH:24]=3)=[C:18]([F:32])[CH:17]=2)[C:8]([C:10]2([C:13]([NH2:15])=[O:14])[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[N:35]1C=CC=CC=1.O.FC(F)(F)C(=O)OI(C1C=CC=CC=1)OC(C(F)(F)F)=O>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH2:35])[CH:24]=3)=[C:18]([F:32])[CH:17]=2)[C:8]([C:10]2([C:13]([NH2:15])=[O:14])[CH2:11][CH2:12]2)=[O:9])=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 102317Bis(trifluoroacetoxy)iodobenzeneHCID 60209292HCID 60209292, compound

Product 1

HCID 11704806HCID 11704806, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(4-fluorobenzyl)-N-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenyl)cyclopropane-1,1-dicarboxamide (25 mg, 0.05 mmol) in DMF (1 mL) at room temperature was added pyridine (0.2 mL), water (0.1 mL), and [bis(trifluoroacetoxyl)-iodo]benzene (Aldrich, 34 mg, 0.08 mmol). The reaction mixture was stirred at rt for 2 h, and then quenched by adding 2 mL of methanol. The reaction mixture was purified by prep. HPLC. The desired fractions were combined, neutralized with aq. K2HPO4, concentrated and extracted with ethyl acetate. The organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was dissolved in a small amount of CH3CN/H2O and lyophillized to dryness to give the title comopound (21 mg, 90%) as a white solid. 1H NMR (DMSO-d6) δ 10.87 (br s, 1H), 8.44 (t, 1H, J=6.0 Hz), 7.91 (d, 1H, J=6.6 Hz), 7.88 (d, 1H, J=13.2 Hz), 7.37-7.29 (m, 6H), 7.13 (t, 2H, J=8.8 Hz), 4.29 (d, 2H, J=6.1 Hz), 1.38 (d, 4H, J=2.2 Hz); MS(ESI+) m/z 439.14 (M+H)+.

Workup

  1. customquenched
  2. additionby adding 2 mL of methanol
  3. customThe reaction mixture was purified by prep
  4. concentrationconcentrated
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic extracts were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in a small amount of CH3CN/H2O
  9. customto give the title comopound (21 mg, 90%) as a white solid

Sources & evidence

ORD record
ord-f832d582db234b61bebf724a70002fba
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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