2-Fluoro-4-iodoaniline → 7-chloro-6-(2-fluoro-4-iodophenylamino)-3-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylic acid

HRID 558216Notes

Reaction equation

HRID 558216 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[C:21]1[C:22]([Cl:34])=[C:23]2[N:32]=[CH:31][N:30]([CH3:33])[C:24]2=[N:25][C:26]=1[C:27]([OH:29])=[O:28]>C1COCC1>[Cl:34][C:22]1[C:21]([NH:4][C:3]2[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:2]=2[F:1])=[C:26]([C:27]([OH:29])=[O:28])[N:25]=[C:24]2[N:30]([CH3:33])[CH:31]=[N:32][C:23]=12

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 669992926-bromo-7-chloro-3-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylic acid

Product 1

HCID 595194827-chloro-6-(2-fluoro-4-iodophenylamino)-3-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-fluoro-4-iodo-aniline (2.9 g, 22.1 mmol) in THF (20 ml) at −78° C. is added LiHMDS (33.3 ml, 1 M in THF, 33.3 mmol) dropwise. The reaction mixture is stirred for 10 min and a solution of 6-bromo-7-chloro-3-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylic acid (WO 2005/051906) (5.63 g, 10.1 mmol) in THF (30 ml) is added to the mixture. The reaction is slowly warmed to room temperature and stirred at this temperature for 16 h. The mixture is concentrated, quenched with 10% HCl solution (70 ml), and extracted with EtOAc (2×200 ml). The combined organic solution is dried over MgSO4 and concentrated to dryness. Purification by trituration with boiling CH2Cl2 gives the title compound.

Workup

  1. stirringstirred at this temperature for 16 h
  2. concentrationThe mixture is concentrated
  3. customquenched with 10% HCl solution (70 ml)
  4. extractionextracted with EtOAc (2×200 ml)
  5. dry with materialThe combined organic solution is dried over MgSO4
  6. concentrationconcentrated to dryness
  7. customPurification by trituration with boiling CH2Cl2

Sources & evidence

ORD record
ord-1d0da4f8246d41b1843f60aabc7b450a
Source dataset
uspto-grants-2011_11
Patent number
US08063049B2

Reaction notes

Loading…