Hydrochloric Acid → (2-Bromo-pyridin-4-yl)-[5-(4-dimethylamino-piperidin-1-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-methanone

HRID 1909025Notes

Reaction equation

HRID 1909025 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([C:10]2[NH:14][C:13]3[CH:15]=[CH:16][C:17]([N:19]4[CH2:24][CH2:23][CH:22]([N:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]4)=[CH:18][C:12]=3[N:11]=2)=[O:9])[CH:5]=[CH:4][N:3]=1.[H-].[Na+].[CH3:30][Si:31]([CH3:38])([CH3:37])[CH2:32][CH2:33][O:34][CH2:35]Cl.Cl>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([C:10]2[N:14]([CH2:35][O:34][CH2:33][CH2:32][Si:31]([CH3:38])([CH3:37])[CH3:30])[C:13]3[CH:15]=[CH:16][C:17]([N:19]4[CH2:20][CH2:21][CH:22]([N:25]([CH3:27])[CH3:26])[CH2:23][CH2:24]4)=[CH:18][C:12]=3[N:11]=2)=[O:9])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178482920HCID 178482920, compound

Product 1

HCID 86664348(2-Bromo-pyridin-4-yl)-[5-(4-dimethylamino-piperidin-1-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-methanoneYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(2-Bromo-pyridin-4-yl)-[5-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone (11.9 g, 27.8 mmol) was dissolved in 200 mL of dry THF. This solution was cooled at 0° C. and NaH 60% dispersion (1.34 g, 33.3 mmol) was added in portions. The mixture stirred at 0° C. for 30 minutes and then the 2-(trimethylsilyl)ethoxymethyl chloride (5.56 g, 33.3 mmol) was added dropwise. The mixture was allowed to warm at room temperature while stirring overnight. 2M Aqueous HCl (300 mL) was carefully added and then the aqueous mixture was washed with EtOAc (3×100 mL). The aqueous phase was then neutralised with saturated aqueous NaHCO3 and then extracted with CHCl3/iPrOH (3:1; 3×250 mL). The combined CHCl3/i-PrOH fractions were dried (Na2SO4) and then evaporated to dryness. Purification by SiO2 chromatography (dichloromethane/NH3 2.0M in MeOH; 98:2 to 90:10) gave the title compound as a dark red oil (11.2 g, yield 72%; as a mixture of two regioisomers). MS(ESI) m/z 558, 560.2 (M+H)+.

Workup

  1. temperatureto warm at room temperature
  2. stirringwhile stirring overnight
  3. washthe aqueous mixture was washed with EtOAc (3×100 mL)
  4. extractionextracted with CHCl3/iPrOH (3:1; 3×250 mL)
  5. dry with materialThe combined CHCl3/i-PrOH fractions were dried (Na2SO4)
  6. customevaporated to dryness
  7. customPurification by SiO2 chromatography (dichloromethane/NH3 2.0M in MeOH; 98:2 to 90:10)

Sources & evidence

ORD record
ord-834f7c28ed3046a382c23d8c7ef6c83e
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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