Water → HCID 11704806, compound

HRID 1670349Notes

Reaction equation

HRID 1670349 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, compoundYield 90%

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 compound (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

Sources & evidence

ORD record
ord-662226da034c4a2ea7c8041672d4a05f
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

Loading…