Sodium hydride → 7-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[2,3-b]-pyrazine

HRID 1052269Notes

Reaction equation

HRID 1052269 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([CH2:11][CH2:12][C:13]3[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=3)[N:9]=2)[NH:4][C:3]=1[C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[CH:25][CH:24]=1.[H-].[Na+].[CH3:38][Si:39]([CH3:46])([CH3:45])[CH2:40][CH2:41][O:42][CH2:43]Cl>O1CCCC1>[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([CH2:11][CH2:12][C:13]3[CH:14]=[C:15]([O:21][CH3:22])[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=3)[N:9]=2)[N:4]([CH2:43][O:42][CH2:41][CH2:40][Si:39]([CH3:46])([CH3:45])[CH3:38])[C:3]=1[C:23]1[CH:24]=[CH:25][C:26]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 730571517-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 899624757-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[2,3-b]-pyrazineYield 40.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 7-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine (from Example 46, 110 mg, 0.205 mmol) in tetrahydrofuran (2 mL), sodium hydride (12.0 mg, 0.300 mmol) was added at 0° C. After 10 min, [β-(trimethylsilyl)ethoxy]methyl chloride (55.7 μL, 0.315 mmol) was added dropwise. After another 1 hour, the reaction was quenched with saturated aqueous NH4Cl, extracted with methylene chloride. The combined organic layers were dried over MgSO4, and then concentrated. The residue was purified on silica gel (eluting with 0 to 8% MeOH in DCM) to give the desired product (55 mg, 31%). LCMS calculated for C33H45BrN5O3Si (M+H)+: m/z=666.2. Found: 666.3.

Workup

  1. waitAfter another 1 hour
  2. customthe reaction was quenched with saturated aqueous NH4Cl
  3. extractionextracted with methylene chloride
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified on silica gel (eluting with 0 to 8% MeOH in DCM)

Sources & evidence

ORD record
ord-5edb2341ce4e48c284e54c9d28fab4c7
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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