4-Fluoroaniline → N-[4-[[2-(Aminocarbonyl)-4-pyridinyl]oxy]-2,5-difluorophenyl]-N′-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide

HRID 2265712Notes

Reaction equation

HRID 2265712 reaction equation
[C:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[C:16]([F:17])=[CH:15][C:14]([NH:18][C:19]([C:21]3([C:24]([OH:26])=O)[CH2:23][CH2:22]3)=[O:20])=[C:13]([F:27])[CH:12]=2)[CH:7]=[CH:6][N:5]=1)(=[O:3])[NH2:2].[F:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>O1CCCC1>[NH2:2][C:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[C:16]([F:17])=[CH:15][C:14]([NH:18][C:19]([C:21]3([C:24]([NH:33][C:32]4[CH:34]=[CH:35][C:29]([F:28])=[CH:30][CH:31]=4)=[O:26])[CH2:23][CH2:22]3)=[O:20])=[C:13]([F:27])[CH:12]=2)[CH:7]=[CH:6][N:5]=1)=[O:3]

Participants

5

Reactant 3

HCID 97314-FluoroanilineHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 68690514HCID 68690514, compound

Product 1

HCID 59597002N-[4-[[2-(Aminocarbonyl)-4-pyridinyl]oxy]-2,5-difluorophenyl]-N′-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-[4-(2-carbamoylpyridin-4-yl)oxy-2,5-difluorophenylaminocarbonyl]cyclopropanecarboxylic acid (100 mg) and 4-fluoroaniline (0.051 ml) in tetrahydrofuran (4 ml) was added 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (157 mg), followed by stirring at room temperature 23 hr. The reaction mixture was partitioned between ethyl acetate and an aqueous solution of sodium hydrogencarbonate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=10:1), and fractions containing the target compound were concentrated under reduced pressure. The residue was dried under reduced pressure to provide the titled compound as a white solid (133.5 mg, quant.).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationThe solvent was concentrated under reduced pressure
  5. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  6. additionheptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=10:1), and fractions containing the target compound
  7. concentrationwere concentrated under reduced pressure
  8. customThe residue was dried under reduced pressure

Sources & evidence

ORD record
ord-d04ff8eccac6470d8e6590aab2da0665
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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