Water → 2-bromo-N-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-[(2-fluoro-4-iodophenyl)-amino]isonicotinamide

HRID 78828Notes

Reaction equation

HRID 78828 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[CH:9][N:10]=1)[C:5]([OH:7])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:32][C:33]1([CH3:41])[O:37][CH:36]([CH2:38][O:39][NH2:40])[CH2:35][O:34]1.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[CH:9][N:10]=1)[C:5]([NH:40][O:39][CH2:38][C@H:36]1[CH2:35][O:34][C:33]([CH3:41])([CH3:32])[O:37]1)=[O:7]

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 10240948O-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]hydroxylamineHCID 576496492-Bromo-5-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid

Product 1

HCID 866291922-bromo-N-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-[(2-fluoro-4-iodophenyl)-amino]isonicotinamideYield 55.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-bromo-N-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide was synthesized as described in General Method 3: to a solution of 2-bromo-5-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid (145.0 mg, 0.33 mmol) in DMF (1.5 ml) was added 1,1′-carbonylbis(1H-imidazole) (60 mg, 0.36 mmol). The reaction mixture was stirred at room temperature under argon for 6 hrs. Then, O-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]hydroxylamine (125 mg, 0.83 mmol) was added, and stirred overnight. The reaction mixture was poured into water (10 ml). Extracted with EtOAc (3×15 ml), the combined organic layer was washed with brine (2×15 ml), and dried over MgSO4. The solvent was evaporated, and the residue was purified on silica gel column (Hex:EtOAc=3:1) to obtain 104 mg (55%) of 2-bromo-N-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-[(2-fluoro-4-iodophenyl)-amino]isonicotinamide. LC/MS: 10.43 min, 566, 568.

Workup

  1. custom2-bromo-N-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide was synthesized
  2. stirringstirred overnight
  3. extractionExtracted with EtOAc (3×15 ml)
  4. washthe combined organic layer was washed with brine (2×15 ml)
  5. dry with materialdried over MgSO4
  6. customThe solvent was evaporated
  7. customthe residue was purified on silica gel column (Hex:EtOAc=3:1)

Sources & evidence

ORD record
ord-eec52822045547188936d1d276b59875
Source dataset
uspto-grants-2014_09
Patent number
US08841459B2

Reaction notes

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