Sodium hydride → 1-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]eth-2-yl (3-Phenylprop-2-ynyl) Ether

HRID 1008007Notes

Reaction equation

HRID 1008007 reaction equation
[H-].[Na+].[CH3:3][C:4]1[N:5]([CH2:22][CH2:23][OH:24])[C:6]2[C:11]([CH3:12])=[C:10]([CH3:13])[N:9]=[C:8]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]=2[N:21]=1.Br[CH2:26][C:27]#[C:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C)C=O>[C:29]1([C:28]#[C:27][CH2:26][O:24][CH2:23][CH2:22][N:5]2[C:6]3[C:11]([CH3:12])=[C:10]([CH3:13])[N:9]=[C:8]([O:14][C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:7]=3[N:21]=[C:4]2[CH3:3])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride3×HCID 10987157(3-Bromoprop-1-yn-1-yl)benzene2×HCID 219131391-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]ethan-2-ol

Product 1

HCID 211004741-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]eth-2-yl (3-Phenylprop-2-ynyl) EtherYield 67.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Sodium hydride (0.82 g, 20.48 mmol, 60% in mineral oil) and anhydrous N,N-dimethylformamide (20 mL) were combined and stirred for 5 minutes under nitrogen. A solution of 1-[2,6,7-trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]ethan-2-ol (5.8 g, 19.50 mmol) from Part G in N,N-dimethylformamide (30 mL) was then added to the sodium hydride over 5 minutes. After stirring the resulting reaction solution for 10 minutes at room temperature, a solution of 3-bromo-1-phenylpropyne (4.18 g, 21.45 mmol) from Part A in N,N-dimethylformamide (15 mL) was added to the reaction solution, and the resulting reaction mixture was stirred for 4 hours and 10 minutes. Sodium hydride (0.10 g, 60 % in mineral oil) and then 3-bromo-1-phenylpropyne (1 g) were added to the reaction mixture, and after stirring for 30 minutes, HPLC monitoring of the reaction mixture indicated about 7% starting material remaining. The reaction mixture was concentrated under reduced pressure, and the resulting oil was dissolved in dichloromethane. The dichloromethane solution was washed with saturated ammonium chloride (3×), water (3×), and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a brown solid, which was triturated with diethyl ether. The resulting solid was filtered off, and a second crop was collected from the mother liquor. The combined solids were passed through a column of silica (120 g, 40×200 mm) using 95/5 ethyl acetate/dichloromethane. A white solid (5.4 g) was isolated and carried on to the next step. HPLC analysis indicated the presence of about 9% starting material in the white solid.

Workup

  1. stirringAfter stirring
  2. customthe resulting reaction solution for 10 minutes at room temperature
  3. customthe resulting reaction mixture
  4. stirringwas stirred for 4 hours and 10 minutes
  5. stirringafter stirring for 30 minutes
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. dissolutionthe resulting oil was dissolved in dichloromethane
  8. washThe dichloromethane solution was washed with saturated ammonium chloride (3×), water (3×), and brine (3×)
  9. dry with materialdried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to a brown solid, which
  12. customwas triturated with diethyl ether
  13. filtrationThe resulting solid was filtered off
  14. customa second crop was collected from the mother liquor

Sources & evidence

ORD record
ord-2de5a15694c4417eaa6c533fa4e6da33
Source dataset
uspto-grants-2004_09
Patent number
US06797718B2

Reaction notes

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