2-Bromopyridine → 6-Chloro-3-nitro-2-(pyridine-2-carbonyl)indole

HRID 379823Notes

Reaction equation

HRID 379823 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[Cl:13][C:14]1[CH:22]=[C:21]2[C:17]([C:18]([N+:29]([O-:31])=[O:30])=[C:19]([C:23](N(OC)C)=[O:24])[NH:20]2)=[CH:16][CH:15]=1.[Cl-].[NH4+].C(=O)(O)[O-].[Na+]>C(OCC)C.C1COCC1>[Cl:13][C:14]1[CH:22]=[C:21]2[C:17]([C:18]([N+:29]([O-:31])=[O:30])=[C:19]([C:23]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)=[O:24])[NH:20]2)=[CH:16][CH:15]=1

Participants

8

Reactant 5

HCID 79732-BromopyridineHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 183681976-Chloro-2-(N-methoxy-N-methylamino)carbonyl-3-nitroindoleHCID 178418339Butyllithium

Product 1

HCID 183678596-Chloro-3-nitro-2-(pyridine-2-carbonyl)indoleYield 43%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromopyridine (548 mg, 3.47 mmol) in diethyl ether (8 ml) cooled to −70° C. was added dropwise 1.66 M n-BuLi (2.1 ml in hexane). After stirring for 30 min, a solution of 6-chloro-2-(N-methoxy-N-methylamino)carbonyl-3-nitroindole (step 2, 328 mg, 1.16 mmol) in THF (8 ml) was added. The mixture was allowed to warm to ambient temperature and stirring continued for 5 h. Saturated ammonium chloride (20 ml) was then added and the mixture basified with saturated sodium bicarbonate (50 ml). The mixture was extracted with ethyl acetate (150 ml) and the extract was washed with brine (80 ml) and dried (Na2SO4). After removal of solvent by evaporation, the residue was purified by flash column chromatography eluting with ethyl acetate/hexane (1:3) to afford 150 mg (43%) of the title compound.

Workup

  1. stirringstirring
  2. waitcontinued for 5 h
  3. extractionThe mixture was extracted with ethyl acetate (150 ml)
  4. washthe extract was washed with brine (80 ml)
  5. dry with materialdried (Na2SO4)
  6. customAfter removal of solvent
  7. customby evaporation
  8. customthe residue was purified by flash column chromatography
  9. washeluting with ethyl acetate/hexane (1:3)

Sources & evidence

ORD record
ord-9ccc4ca1a31949898bb53e922f623e11
Source dataset
uspto-grants-2001_10
Patent number
US06300363B1

Reaction notes

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