Methanol → 1-(3-Bromophenyl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amine

HRID 1662193Notes

Reaction equation

HRID 1662193 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH:13]([F:15])[F:14])[CH:8]=1.[Br:16][C:17]1[CH:18]=[C:19]([C:23]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[C:38]#[N:39])=[N:24]S(C(C)(C)C)=O)[CH:20]=[CH:21][CH:22]=1.CO>C1COCC1>[Br:16][C:17]1[CH:18]=[C:19]([C:23]2([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([CH:13]([F:15])[F:14])[CH:8]=3)[C:31]3[C:32](=[C:33]([F:37])[CH:34]=[CH:35][CH:36]=3)[C:38]([NH2:39])=[N:24]2)[CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 585795394-Bromo-2-(difluoromethyl)pyridineHCID 76821598N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 585795251-(3-Bromophenyl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amineYield 18.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (0.254 mL, 0.63 mmol) was dropwise added to 4-bromo-2-(difluoromethyl)pyridine (120 mg, 0.58 mmol) in anhydrous THF (5.00 mL) at −78° C. under argon atmosphere. The reaction mixture was stirred for 25 min. N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (235 mg, 0.58 mmol) in anhydrous THF (5.00 mL) was dropwise added. The reaction mixture was stirred for 2 h, then methanol (5 mL) was added and the temperature was allowed to reach room temperature. The reaction mixture was partitioned between aqueous ammonium chloride and ethyl acetate. The aqueous phase was extracted with ethyl acetate (×3). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by prep. HPLC to afford the title compound (47.1 mg, 18%).

Workup

  1. stirringThe reaction mixture was stirred for 2 h
  2. customto reach room temperature
  3. customThe reaction mixture was partitioned between aqueous ammonium chloride and ethyl acetate
  4. extractionThe aqueous phase was extracted with ethyl acetate (×3)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep

Sources & evidence

ORD record
ord-6efaf476fe7c41658f2105da209f2890
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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