1-Bromo-2-Chloroethane → HCID 67147439, compound

HRID 490482Notes

Reaction equation

HRID 490482 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[OH:12])[N:8]([CH3:13])[CH:7]=[C:6]2[C:14]1[N:22]([S:23]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:17]2=[N:18][CH:19]=[CH:20][CH:21]=[C:16]2[CH:15]=1.[H-].[Na+].Br[CH2:36][CH2:37][Cl:38].C1CCCCC1.C(OCC)(=O)C>CN(C)C=O.O.C(OCC)(=O)C>[Cl:38][CH2:37][CH2:36][O:12][C:11]1[CH:10]=[C:9]2[C:5]([C:6]([C:14]3[N:22]([S:23]([C:26]4[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=4)(=[O:25])=[O:24])[C:17]4=[N:18][CH:19]=[CH:20][CH:21]=[C:16]4[CH:15]=3)=[CH:7][N:8]2[CH3:13])=[CH:4][C:3]=1[O:2][CH3:1]

Participants

8

Reactant 4

HCID 78491-Bromo-2-Chloroethane2×HCID 24758Sodium hydride2×HCID 21867204Cyclohexane ethylacetateHCID 22477326HCID 22477326, compound

Product 1

HCID 67147439HCID 67147439, compoundYield 72.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 5-methoxy-1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-6-ol (0.8 g; 1.788 mmol) in solution in dimethylformamide (5 ml) is placed in a 50 ml round-bottomed flask rendered inert with argon, and sodium hydride (0.064 g; 2.146 mmol) is then added. The reaction mixture becomes brown in color and 1-bromo-2-chloroethane (0.308 g; 2.146 mmol) is added. The reaction mixture is agitated for 1 hour 30 minutes at 20° C. and then sodium hydride (0.064 g; 2.146 mmol) and 1-bromo-2-chloroethane (2×0.5 ml) are again added. Analysis by thin layer chromatography (50/50 cyclohexane/ethyl acetate) shows that the reaction has come to an end. The reaction mixture is diluted with water (150 ml) and ethyl acetate (50 ml), and extracted with ethyl acetate (2×50 ml). The organic extracts are combined, dried over magnesium sulfate, filtered, and evaporated under reduced pressure, resulting in the crude compound, which is purified by chromatography on silica gel (AIT cartridge FC 25 Si-BP-Sup, eluent: 65/35 cyclohexane/ethyl acetate at 10 ml/min). The fractions containing the expected compound are combined and then evaporated under reduced pressure, giving the expected 2-[6-(2-chloroethoxy)-5-methoxy-1-methyl-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (0.66 g; 72%) in the form of a powder, the characteristics of which are as follows:

Workup

  1. additionis then added
  2. additionis added
  3. extractionextracted with ethyl acetate (2×50 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customresulting in the crude compound, which
  8. customis purified by chromatography on silica gel (AIT cartridge FC 25 Si-BP-Sup, eluent: 65/35 cyclohexane/ethyl acetate at 10 ml/min)
  9. additionThe fractions containing the expected compound
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-7ab6357edffa4d72b4f3e3007088a59e
Source dataset
uspto-grants-2009_05
Patent number
US07528147B2

Reaction notes

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