Sodium hydride → phenylmethyl{[6-bromo-3-({[2-(trimethylsilyl)ethyl]oxy}methyl)-3H-imidazo[4,5-b]pyridin-2-yl]methyl}methylcarbamate

HRID 241027Notes

Reaction equation

HRID 241027 reaction equation
[C:1]1([CH2:7][O:8][C:9](=[O:23])[N:10]([CH2:12][C:13]2[NH:14][C:15]3[C:16]([N:22]=2)=[N:17][CH:18]=[C:19]([Br:21])[CH:20]=3)[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:26][Si:27]([CH3:34])([CH3:33])[CH2:28][CH2:29][O:30][CH2:31]Cl>CN(C)C=O>[C:1]1([CH2:7][O:8][C:9](=[O:23])[N:10]([CH2:12][C:13]2[N:22]([CH2:31][O:30][CH2:29][CH2:28][Si:27]([CH3:34])([CH3:33])[CH3:26])[C:16]3=[N:17][CH:18]=[C:19]([Br:21])[CH:20]=[C:15]3[N:14]=2)[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 66820271HCID 66820271, compound

Product 1

HCID 66820472phenylmethyl{[6-bromo-3-({[2-(trimethylsilyl)ethyl]oxy}methyl)-3H-imidazo[4,5-b]pyridin-2-yl]methyl}methylcarbamateYield 93.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of phenylmethyl[(6-bromo-1H-imidazo[4,5-b]pyridin-2-yl)methyl]methylcarbamate (0.22 g, 0.59 mmol) in N,N-dimethylformamide (3.0 mL) was added 60% sodium hydride in mineral oil (56 mg, 1.48 mmol) and the reaction mixture was stirred for 30 minutes at room temperature, followed by the addition of 2-(trimethylsilyl)ethoxymethyl chloride (0.11 mL, 0.62 mmol). The reaction mixture was stirred at room temperature for 16 hours then it was quenched by the careful addition of saturated aqueous ammonium chloride and partitioned with ethyl acetate (20 mL) and water (20 mL). The organic layer was separated and washed with 10% aqueous citric acid (2×20 mL) and brine (20 mL), dried over sodium sulfate, filtered and concentrated. Gradient flash chromatography (15% to 35% ethyl acetate in hexane) gave phenylmethyl{[6-bromo-3-({[2-(trimethylsilyl)ethyl]oxy}methyl)-3H-imidazo[4,5-b]pyridin-2-yl]methyl}methylcarbamate (0.28 g, 93%). MS (EI) for C22H29BrN4O3Si: 506 (MH+).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 16 hours
  2. customit was quenched by the careful addition of saturated aqueous ammonium chloride
  3. custompartitioned with ethyl acetate (20 mL) and water (20 mL)
  4. customThe organic layer was separated
  5. washwashed with 10% aqueous citric acid (2×20 mL) and brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-538a8bb0b5624846bab00d59b8288f70
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

Loading…