Sodium hydride → 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine

HRID 1854462Notes

Reaction equation

HRID 1854462 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[CH:10]=[C:9]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13]([CH3:22])[CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:25][Si:26]([CH2:29][CH2:30][O:31][CH2:32]Cl)([CH3:28])[CH3:27]>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[CH:10]=[C:9]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13]([CH3:22])[CH:12]=3)[N:8]([CH2:32][O:31][CH2:30][CH2:29][Si:26]([CH3:28])([CH3:27])[CH3:25])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 498306752-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 580101552-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazineYield 89.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine (0.500 g, 1.40 mmol) in DMF (15 mL) was cooled to about 0° C. then treated with NaH (60% dispersion in mineral oil, 0.112 g, 2.80 mmol). The mixture was stirred for about 15 min, SEM-Cl (0.372 mL, 2.10 mmol) was added, and the mixture was warmed to ambient temperature for about 15 min. The mixture was concentrated and purified by silica gel chromatography (40 g silica column) eluting with DCM to give 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.61 g, 89%): LC/MS (Table 2, Method a) Rt=3.88 min; MS m/z: 489 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by silica gel chromatography (40 g silica column)
  3. washeluting with DCM

Sources & evidence

ORD record
ord-00081c26d323497097550e525c398014
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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