Bromine → 8-bromo-1-chloro-5H-pyrido[4,3-b]indole-4-carboxamide

HRID 1896519Notes

Reaction equation

HRID 1896519 reaction equation
[Cl:1][C:2]1[C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:15]([NH2:17])=[O:16])=[CH:4][N:3]=1.[Br:18]Br.C1COCC1.CCOC(C)=O.C([O-])(O)=O.[Na+]>CC(O)=O.C1COCC1.[Zn]>[Br:18][C:11]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[C:5]([C:15]([NH2:17])=[O:16])=[CH:4][N:3]=[C:2]([Cl:1])[C:14]=3[C:13]=2[CH:12]=1

Participants

8

Reactant 4

HCID 24408BromineHCID 516892Sodium BicarbonateHCID 21939870Tetrahydrofuran ethyl acetateHCID 591984571-chloro-5H-pyrido[4,3-b]indole-4-carboxamide

Product 1

HCID 591984248-bromo-1-chloro-5H-pyrido[4,3-b]indole-4-carboxamide

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-chloro-5H-pyrido[4,3-b]indole-4-carboxamide (Example 10 Step 3) in AcOH (0.15 M) at room temperature was added Br2 (10 equiv) to provide a homogeneous mixture. After standing at room temperature a precipitate formed, and after 1 h, a suspension of Zn powder (excess) in THF was added in a cold water bath. After a period of 10 min, the reaction mixture was poured over THF/EtOAc and saturated NaHCO3. After separation of the organic phase, the aqueous phase was extracted again with THF/EtOAc, and the combined organic phases were washed with brine, dried over MgSO4 and filtered. After evaporation of the organic solvents, the residue was purified by flash chromatography (10-70% EtOAc in hexanes) to provide the title compound as a yellow solid.

Workup

  1. customto provide a homogeneous mixture
  2. customAfter standing at room temperature
  3. customformed
  4. additionwas added in a cold water bath
  5. waitAfter a period of 10 min
  6. customAfter separation of the organic phase
  7. extractionthe aqueous phase was extracted again with THF/EtOAc
  8. washthe combined organic phases were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customAfter evaporation of the organic solvents
  12. customthe residue was purified by flash chromatography (10-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2dabf5fac70349189fae302fb07f44e3
Source dataset
uspto-grants-2013_08
Patent number
US08518964B2

Reaction notes

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