Trifluoroacetic acid → N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476375Notes

Reaction equation

HRID 476375 reaction equation
COC1C=CC(C[NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]4([C:28]([NH:30][C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)=[O:29])[CH2:27][CH2:26]4)=[O:24])=[C:18]([F:38])[CH:17]=3)[CH:12]=[CH:11][N:10]=2)=CC=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]3([C:28]([NH:30][C:31]4[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=4)=[O:29])[CH2:27][CH2:26]3)=[O:24])=[C:18]([F:38])[CH:17]=2)[CH:12]=[CH:11][N:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66604557N-(4-(2-(4-methoxybenzylamino)pyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 59596943N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 42.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N-(4-(2-(4-methoxybenzylamino)pyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (160 mg, 0.29 mmol) in CH2Cl2 (0.2 mL) was treated with trifluoroacetic acid (0.4 mL, 5.26 mmol) and the resultant mixture was stirred overnight at RT. The reaction mixture was concentrated to dryness and the residue was purified by reverse-phase silica gel chromatography (25-95% acetonitrile in water, 0.1% TFA). The desired fractions were partitioned between saturated aqueous NaHCO3 and EtOAc. The organics were washed with saturated aqueous NaHCO3, water, and brine and were dried over Na2SO4 and concentrated in vacuo to provide N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (52 mg, 39% yield). MS (ESI) m/z: 425.1 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue was purified by reverse-phase silica gel chromatography (25-95% acetonitrile in water, 0.1% TFA)
  3. customThe desired fractions were partitioned between saturated aqueous NaHCO3 and EtOAc
  4. washThe organics were washed with saturated aqueous NaHCO3, water, and brine
  5. dry with materialwere dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fb65a14fee9c4a0ca829b9a1e0db0c30
Source dataset
uspto-grants-2014_01
Patent number
US08637672B2

Reaction notes

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