1,2-Dimethoxyethane → HCID 22330121, compound

HRID 324745Notes

Reaction equation

HRID 324745 reaction equation
[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13](C4CCCN(C)C4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:28]([CH2:31]OC)OC>>[C:1]([C:4]1[CH:25]=[CH:24][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:8]4[CH2:31][CH2:28][NH:10][CH2:6][CH2:7]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 14798Sodium HydroxideHCID 227418345-Acetyl-1-[3-(1-methylpiperidin-3-yl)phenyl]benzimidazole

Product 1

HCID 22330121HCID 22330121, compoundYield 65%

Conditions

Temperature
80 °C

Procedure

To a solution of 5-acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole (see Example 12) (8.3 g, 23.0 mmol) in dimethoxyethane (140 ml) was added aqueous sodium hydroxide (70 ml, 1M) and the mixture was heated to 80° C. overnight. The organic solvent was removed under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic phase was concentrated and purified by column-chromatography on silica gel using a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v/v/v) as the eluent. The concentrated eluate was triturated with diethyl ether to yield 5-acetyl-1-(3-(piperazin-1-yl)phenyl)benzimidazole (4.81 g, 65%) as red crystals. This product (2.0 g, 6.25 mmol) was dissolved in refluxing ethanol (20 ml). O-isopropylhydroxylamine, hydrochloride (0.7 g, 6.25 mmol) was added and reflux was continued for 5 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between aqueous sodium hydroxide (1M) and dichloromethane. The organic phase was dried and concentrated and eluted through silica gel with a mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v/v/v) to yield 5-acetyl-1-(3-(1-piperazinyl)phenyl)-benzimidazole O-i-propyl oxime (1.75 g, 74%). This product was alkylated with methyl bromoacetate in anhydrous DMF on the presence of triethylamine at room temperature to yield 5f1 (0.48 g, 77%). M.p. 120-121° C.

Workup

  1. customThe organic solvent was removed under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionextracted with dichloromethane
  4. concentrationThe organic phase was concentrated
  5. custompurified by column-chromatography on silica gel using
  6. additiona mixture of dichloromethane, methanol and aqueous ammonia (90:10:1 v/v/v) as the eluent
  7. customThe concentrated eluate was triturated with diethyl ether

Sources & evidence

ORD record
ord-dff5feb3a030455a92fbd7d37a9a0070
Source dataset
uspto-grants-2001_04
Patent number
US06218547B1

Reaction notes

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