Methyl iodide → 1-Benzenesulfonyl-4-bromo-2-methyl-1H-pyrrolo[3,2-c]pyridine

HRID 1945581Notes

Reaction equation

HRID 1945581 reaction equation
[C:1]1([S:7]([N:10]2[C:18]3[CH:17]=[CH:16][N:15]=[C:14]([Br:19])[C:13]=3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:20]([N-]C(C)C)(C)C.[Li+].CI>C1COCC1>[C:1]1([S:7]([N:10]2[C:18]3[CH:17]=[CH:16][N:15]=[C:14]([Br:19])[C:13]=3[CH:12]=[C:11]2[CH3:20])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 57506731HCID 57506731, compound

Product 1

HCID 596057611-Benzenesulfonyl-4-bromo-2-methyl-1H-pyrrolo[3,2-c]pyridineYield 96.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-35 °C

Procedure

A 50 mL round-bottomed flask, under nitrogen, fitted with a thermometer probe and a condenser/inert gas bubbler (via a Claisen head) was charged with a solution of 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (0.43 g, 1.27 mmol) in anhydrous THF (8 mL). To the resultant solution, at −35° C., was added dropwise a solution of lithium diisopropylamide (2.0M in heptane/THF/ethyl benzene, 1.27 mL, 2.54 mmol) and the mixture was stirred at −35° C. for 30 min. Methyl iodide (0.48 mL, 7.63 mmol) was added dropwise and solution was allowed to reach room temperature and stirred for 3 h. The reaction was quenched by addition of 1N HCl (3 mL). The solution was diluted with water (7 mL), extracted with EtOAc (2×50 mL). The organic extracts were pooled, was dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, 0-100% EtOAc:cyclohexane) to give the desired product (0.43 g, 96%) as a white powder. LCMS (Method A) RT=4.67 min, [M+H]+ 351 (79Br), 353 (8Br)

Workup

  1. customA 50 mL round-bottomed flask, under nitrogen, fitted with a thermometer probe
  2. customto reach room temperature
  3. stirringstirred for 3 h
  4. customThe reaction was quenched by addition of 1N HCl (3 mL)
  5. additionThe solution was diluted with water (7 mL)
  6. extractionextracted with EtOAc (2×50 mL)
  7. dry with materialwas dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was purified by flash chromatography (Si—PPC, 0-100% EtOAc:cyclohexane)

Sources & evidence

ORD record
ord-01c773c63d30484598b3f5a26b1daca3
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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