2-Fluoro-4-iodoaniline → 4-(2-Fluoro-4-iodophenylamino)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acid

HRID 605674Notes

Reaction equation

HRID 605674 reaction equation
Cl[C:2]1[C:3]([C:10]([OH:12])=[O:11])=[N:4][N:5]([CH3:9])[C:6](=[O:8])[CH:7]=1.[F:13][C:14]1[CH:20]=[C:19]([I:21])[CH:18]=[CH:17][C:15]=1[NH2:16].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCCC1>[F:13][C:14]1[CH:20]=[C:19]([I:21])[CH:18]=[CH:17][C:15]=1[NH:16][C:2]1[C:3]([C:10]([OH:12])=[O:11])=[N:4][N:5]([CH3:9])[C:6](=[O:8])[CH:7]=1

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 666741324-Chloro-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acid

Product 1

HCID 594691014-(2-Fluoro-4-iodophenylamino)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acidYield 130.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-chloro-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acid (350 mg, 1.855 mmol) and 2-fluoro-4-iodoaniline (1.06 g, 4.453 mmol) in tetrahydrofuran (13.3 mL) was sparged with nitrogen for 5 minutes followed by the slow addition of lithium bis(trimethylsilyl)amide, 1.0 M in THF (7.4 mL). The reaction mixture stirred for an additional 4 hours at room temperature. The mixture was quenched with 1 N HCl and concentrated in vacuo. The residue was partitioned between ethyl acetate and 1 N aqueous HCl. The aqueous layer was extracted (3×) with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated to afford 4-(2-fluoro-4-iodophenylamino)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acid (939 mg, 100% yield). 1H NMR (CDCl3): 7.27 (dd, 1H), 7.21 (d, 1H), 6.54 (t, 1H), 4.84 (broad s, 2H), 2.09 (s, 1H), 1.26 (t, 3H); MS (EI) for C12H9N3O3FI: 389 (MH+).

Workup

  1. customThe mixture was quenched with 1 N HCl
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate and 1 N aqueous HCl
  4. extractionThe aqueous layer was extracted (3×) with ethyl acetate
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-ee5a830081664115a9e4d6a3d77929ca
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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