Ammonium Chloride → 2-Trifluoroacetamido-3-phenyl-6-(2,3-difluorobenzoyl)-imidazo[1,2-a]pyridine

HRID 277933Notes

Reaction equation

HRID 277933 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1Br.C([Li])CCC.[F:15][C:16]([F:42])([F:41])[C:17]([NH:19][C:20]1[N:21]=[C:22]2[CH:27]=[CH:26][C:25]([C:28](=[O:33])N(C)OC)=[CH:24][N:23]2[C:34]=1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:18].[NH4+].[Cl-]>C1COCC1>[F:42][C:16]([F:15])([F:41])[C:17]([NH:19][C:20]1[N:21]=[C:22]2[CH:27]=[CH:26][C:25]([C:28](=[O:33])[C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])=[CH:24][N:23]2[C:34]=1[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:18]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 27332601-Bromo-2,3-difluorobenzeneHCID 22626677HCID 22626677, compoundHCID 178418339Butyllithium

Product 1

HCID 226267592-Trifluoroacetamido-3-phenyl-6-(2,3-difluorobenzoyl)-imidazo[1,2-a]pyridineYield 68.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2,3-difluorobromobenzene (471 ml, 4.206 mmol) in dry THF (20 mL) was added a solution of n-butyl lithium (1.6M in hexanes, 2.63 mL) at −78° C. The resulting yellow solution was stirred at the same temperature for 70 minutes, then a solution of 2-trifluoroacetamido-3-phenyl-6-(N-methyl-N-methoxycarbamoyl)imidazo[1,2-a]pyridine (0.500 g, 1.28 mmol) in dry THF (20 mL), was added dropwise via a cannula. The red-orange solution was allowed to warm over 60 minutes. Saturated NH4Cl was added and the mixture was stirred for 25 minutes before extracting with EtOAc. The organic layer was washed with brine, dried (Na2SO4), concentrated in vacuo and purified by column chromatography (CH2Cl2/CH3CN 4/1) to give 390 mg of an orange solid. (69%). MS(FAB), NMR.

Workup

  1. temperatureto warm over 60 minutes
  2. stirringthe mixture was stirred for 25 minutes
  3. extractionbefore extracting with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography (CH2Cl2/CH3CN 4/1)

Sources & evidence

ORD record
ord-c7a2d11d6ca34c91a36a22795103a530
Source dataset
uspto-grants-2002_03
Patent number
US06358971B1

Reaction notes

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