Hydrochloric Acid → 1-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazole dihydrochloride

HRID 2230714Notes

Reaction equation

HRID 2230714 reaction equation
C(OC([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][CH2:21][O:22][CH2:23][CH:24]3[CH2:26][CH2:25]3)[C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:31]>O1CCOCC1>[ClH:31].[ClH:31].[CH:24]1([CH2:23][O:22][CH2:21][CH2:20][N:19]2[C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]=3[N:16]=[C:15]2[N:11]2[CH2:12][CH2:13][CH2:14][NH:8][CH2:9][CH2:10]2)[CH2:25][CH2:26]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 701489134-[1-(2-cyclopropylmethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester

Product 1

HCID 184647271-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazole dihydrochloride

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Treat a solution of 4-[1-(2-cyclopropylmethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.32 g, 0.76 mmol) and dioxane (4 mL) with 4N HCl in dioxane (2.3 mL, 12 equivalents) with stirring. After 90 minutes concentrate to remove the solvent, add 2.5 mL, of dichloromethane and then add ether dropwise with stirring. Repeat the process of concentration, dissolving in dichloromethane (2 mL) and treating the solution with ether and allowing the mixture to stir overnight until a suspension of yellow crystalline material is obtained. Collect the prpeipitate by filtration under argon, wash with ether and dry in vacuo overnight to give 1-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazole dihydrochloride (0.22 g). Treat a slurry of 1-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazole dihydrochloride (0.16 g, 0.42 mmol) and dichloromethane (150 mL) with saturated NaHCO3 solution. Extract the aqueous phase once with dichloromethane (100 mL). Wash the combined dichloromethane phases with water (3×200 mL) and saturated brine (100 mL), dry (MgSO4) the organic phase, filter and concentrate to afford a 1-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazole as a yellow oil (0.10 g).

Workup

  1. concentrationAfter 90 minutes concentrate
  2. customto remove the solvent
  3. additionadd 2.5 mL
  4. stirringof dichloromethane and then add ether dropwise with stirring
  5. concentrationRepeat the process of concentration
  6. dissolutiondissolving in dichloromethane (2 mL)
  7. additiontreating the solution with ether
  8. stirringto stir overnight until a suspension of yellow crystalline material
  9. customis obtained
  10. customCollect the prpeipitate
  11. filtrationby filtration under argon
  12. washwash with ether
  13. customdry in vacuo overnight

Sources & evidence

ORD record
ord-858f04c9d89d4555adcd8491ef2c5db7
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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