1H-Pyrrolo(2,3-b)pyridine → (2-Bromo-1,3-thiazol-5-yl)(1H-pyrrolo[2,3-b]pyridin-3-yl)methanone

HRID 1754696Notes

Reaction equation

HRID 1754696 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:7]([OH:9])=O)=[CH:5][N:6]=1.[NH:10]1[C:14]2=[N:15][CH:16]=[CH:17][CH:18]=[C:13]2[CH:12]=[CH:11]1.[Cl-].[Cl-].[Cl-].[Al+3]>C(Cl)(=O)C(Cl)=O.ClCCl>[Br:1][C:2]1[S:3][C:4]([C:7]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[NH:10][CH:11]=2)=[O:9])=[CH:5][N:6]=1

Participants

6

Reactant 3

HCID 92221H-Pyrrolo(2,3-b)pyridineHCID 27632102-Bromothiazole-5-carboxylic acidHCID 6451240Aluminum(III) Chloride

Product 1

HCID 59593307(2-Bromo-1,3-thiazol-5-yl)(1H-pyrrolo[2,3-b]pyridin-3-yl)methanoneYield 2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 65578Oxalyl chlorideSolvent

Procedure

A suspension of 2-Bromo-thiazole-5-carboxylic acid (98, 0.5 g, 0.002 mol) in oxalyl chloride (3 mL) was stirred at room temperature until it turned into a clear solution. Solvent was removed and the residue was dried over vacuum. A light yellow solid was obtained and was dissolved in dichloromethane (10 mL) and slowly added to a solution of 1H-Pyrrolo[2,3-b]pyridine (1, 0.34 g, 0.0029 mol) in dichloromethane (30 mL) at −10° C. To the mixture was then added aluminum trichloride (2.6 g, 0.019 mol) in one portion with vigorous stirring. The reaction was held at −10° C. for 30 minutes, then allowed to warm to room temperature. The reaction mixture was stirred at ambient temperature overnight. The reaction was quenched with ice-water and acidified with hydrochloric acid (10%) to pH 4. The solution was then extracted with dichloromethane. The organic layer was collected, washed with brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexane to provide the compound as a white solid (99, 12 mg, 2%). MS (ESI) [M−H+]=369.09.

Workup

  1. customSolvent was removed
  2. customthe residue was dried over vacuum
  3. customA light yellow solid was obtained
  4. temperatureto warm to room temperature
  5. stirringThe reaction mixture was stirred at ambient temperature overnight
  6. customThe reaction was quenched with ice-water
  7. extractionThe solution was then extracted with dichloromethane
  8. customThe organic layer was collected
  9. washwashed with brine
  10. dry with materialdried over magnesium sulfate
  11. customAfter removal of solvent
  12. customthe residue was purified by silica gel column chromatography
  13. washeluting with ethyl acetate in hexane

Sources & evidence

ORD record
ord-8d665fa236a94fbeb54d22ed62e6c0a0
Source dataset
uspto-grants-2015_10
Patent number
US09169250B2

Reaction notes

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