Water → N1-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-N2-benzyloxalamide

HRID 2377737Notes

Reaction equation

HRID 2377737 reaction equation
[CH2:1]([NH:8][C:9](=[O:30])[C:10]([NH:12][C:13]1[CH:28]=[CH:27][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20](C(N)=O)[CH:19]=2)=[C:15]([F:29])[CH:14]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[N:32]1C=CC=CC=1.FC(F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O>CN(C=O)C.C(OCC)(=O)C>[NH2:32][C:20]1[CH:19]=[C:18]([O:17][C:16]2[CH:27]=[CH:28][C:13]([NH:12][C:10](=[O:11])[C:9]([NH:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:30])=[CH:14][C:15]=2[F:29])[CH:23]=[CH:22][N:21]=1

Participants

7

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 102317Bis(trifluoroacetoxy)iodobenzeneHCID 587326274-(4-(2-(Benzylamino)-2-oxoacetamido)-2-fluorophenoxy)picolinamide

Product 1

HCID 11955170N1-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-N2-benzyloxalamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-(4-(2-(benzylamino)-2-oxoacetamido)-2-fluorophenoxy)picolinamide (41 mg, 0.10 mmol) in DMF (0.5 mL), water (5 μL, 0.26 mmol), and pyridine (32 μL, 0.39 mmol) was added [bis(trifluoroacetoxy)iodo]benzene (60 mg, 0.14 mmol, Aldrich). After stirring at rt for 2 h, the reaction was diluted with ethyl acetate (20 mL), washed with 10% aqueous lithium chloride solution (2×10 mL) followed by brine (10 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (EtOAc/0-5% MeOH) to give the title compound as a white solid. The solid was suspended in ethyl acetate (3 mL) and 0.5 mL of 1 N HCl in ether was added. The mixture was concentrated in vacuo and the residue was lyophilized from acetonitrile (1 mL)/water (3 mL) to give the HCl salt of the title compound (25 mg, 60%) as a white solid. 1H NMR (DMSO-d6) δ 11.05 (s, 1H), 9.57 (t, 1H, J=6 Hz), 7.96 (dd, 1H, J=12.8, 2 Hz), 7.91 (d, 1H, J=7.2 Hz), 7.81 (br s, 2H), 7.76 (d, 1H, J=8.8 Hz), 7.43 (t, 1H, J=8.8 Hz), 7.29-7.17 (m, 5H), 6.64 (dd, 1H, J=7.2, 2.8 Hz), 6.10 (d, 1H, J=2 Hz), 4.34 (d, 2H, J=6.4 Hz); MS (ESI+) m/z 381.24 (M+H)+.

Workup

  1. washwashed with 10% aqueous lithium chloride solution (2×10 mL)
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography on silica gel (EtOAc/0-5% MeOH)

Sources & evidence

ORD record
ord-0e8536afdd28475babd4323b6c800d8c
Source dataset
uspto-grants-2008_12
Patent number
US07470693B2

Reaction notes

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