Methyl iodide → tert-butyl (6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl(methyl)carbamate

HRID 2409045Notes

Reaction equation

HRID 2409045 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[CH:17][C:5]2=[N:6][C:7]=1[CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13].[H-].[Na+].[CH3:30]I>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[CH:17][C:5]2=[N:6][C:7]=1[CH2:8][N:9]([CH3:30])[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86762618tert-butyl (6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methylcarbamate

Product 1

HCID 86762619tert-butyl (6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl(methyl)carbamateYield 66.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tert-butyl (6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methylcarbamate (300 mg, 0.75 mmol) in THF (5 mL) was added NaH (60% dispersion in mineral oil, 110 mg, 2.25 mmol). After stirring at RT for 30 min, CH3I (320 mg, 2.25 mmol) was added, followed by stirring at RT for 3 h. The reaction mixture was quenched by adding a sat'd. aq.solution of NH4Cl and extracted with EtOAc (30 mL×2). The combined extracts were dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by SiO2 chromatography eluting with a petroleum ether:EtOAc gradient (10:1 to 1:1) to afford 200 mg (66.6%) of tert-butyl (6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl(methyl)carbamate as a brown oil. MS (ESI): m/z=410.3 [M+1]+.

Workup

  1. stirringby stirring at RT for 3 h
  2. customThe reaction mixture was quenched
  3. additionby adding a sat'd
  4. extractionaq.solution of NH4Cl and extracted with EtOAc (30 mL×2)
  5. dry with materialThe combined extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by SiO2 chromatography
  9. washeluting with a petroleum ether

Sources & evidence

ORD record
ord-5c13f45a10a1444cbbc28f8ff4e918f7
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

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