2-Fluoro-4-iodoaniline → 6-Chloro-3-[(2-fluoro-4-iodophenyl)amino]pyridazine-4-carboxylic acid

HRID 2404220Notes

Reaction equation

HRID 2404220 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].Cl[C:11]1[N:12]=[N:13][C:14]([Cl:20])=[CH:15][C:16]=1[C:17]([OH:19])=[O:18].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1.C(OCC)(=O)C>[Cl:20][C:14]1[N:13]=[N:12][C:11]([NH:4][C:3]2[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:2]=2[F:1])=[C:16]([C:17]([OH:19])=[O:18])[CH:15]=1

Participants

6

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 4338043,6-Dichloropyridazine-4-carboxylic acidHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 248220276-Chloro-3-[(2-fluoro-4-iodophenyl)amino]pyridazine-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To solution of 2-fluoro-4-iodoaniline (9.21 g, 38.86 mmol) and 3,6-Dichloro-pyridazine-4-carboxylic acid (10.84 g, 64.77 mmol) in THF (80 mL) at −78° C., was added LiHMDS (5 g, 25.91 mmol). The mixture was allowed to warm to room temperature and stirred for 12 h. The mixture as diluted with ethyl acetate and washed with H2O and brine. The organic layer was dried with solid Na2SO4 and was concentrated. The resulting residue was purified by flash chromatography in silica (25% ethyl acetate-hexane) to give pure product. LC/MS [4.52 min; 394 (M+1)].

Workup

  1. washwashed with H2O and brine
  2. dry with materialThe organic layer was dried with solid Na2SO4
  3. concentrationwas concentrated
  4. customThe resulting residue was purified by flash chromatography in silica (25% ethyl acetate-hexane)
  5. customto give pure product
  6. customLC/MS [4.52 min; 394 (M+1)]

Sources & evidence

ORD record
ord-035fa69e0e2843979a92913b93097c37
Source dataset
uspto-grants-2014_08
Patent number
US08802703B2

Reaction notes

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