Water → N-{4-[(2-Aminopyridin-4-yl)oxy]-3-fluorophenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2265680Notes

Reaction equation

HRID 2265680 reaction equation
[F:1][C:2]1[CH:17]=[C:16]([NH:18][C:19]([C:21]2([C:24](=[O:33])[NH:25][C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH2:23][CH2:22]2)=[O:20])[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7](C(N)=O)[CH:6]=1.O.FC(F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.[N:56]1C=CC=CC=1>CN(C)C=O>[NH2:56][C:7]1[CH:6]=[C:5]([O:4][C:3]2[CH:14]=[CH:15][C:16]([NH:18][C:19]([C:21]3([C:24]([NH:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[O:33])[CH2:23][CH2:22]3)=[O:20])=[CH:17][C:2]=2[F:1])[CH:10]=[CH:9][N:8]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 1049Pyridine2×HCID 102317Bis(trifluoroacetoxy)iodobenzene2×HCID 595969854-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridine-2-carboxamide

Product 1

HCID 59596906N-{4-[(2-Aminopyridin-4-yl)oxy]-3-fluorophenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridine-2-carboxamide (4.81 g) was dissolved in N,N-dimethylformamide (50 ml) under a nitrogen atmosphere, and water (0.5 ml), [bis(trifluoroacetoxy)iodo]benzene (5.17 g) and pyridine (2.57 ml) were added in this order at room temperature, followed by stirring overnight. Water (0.5 ml), [bis(trifluoroacetoxy)iodo]benzene (5.17 g) and pyridine (2.57 ml) were added in this order at room temperature, followed by further stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (200 ml) and water (100 ml). The organic layer was separated, washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure and the residue was dried under reduced pressure to provide the titled compound as pale brown foam (2.878 g, 64%).

Workup

  1. stirringby further stirring for 1 hr
  2. customThe reaction mixture was partitioned between ethyl acetate (200 ml) and water (100 ml)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationThe solvent was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate)
  8. additionFractions containing the target compound
  9. concentrationwere concentrated under reduced pressure
  10. customthe residue was dried under reduced pressure

Sources & evidence

ORD record
ord-4ca7671ee11f462daf5ce47cc41ebd3b
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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