Sodium Hydroxide → HCID 22330121, compound

HRID 49827Notes

Reaction equation

HRID 49827 reaction equation
[C:1]([C:4]1[CH:27]=[CH:26][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:17]4[CH2:22][CH2:21][N:20](C(=O)C)[CH2:19][CH2:18]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+]>C(COC)OC>[C:1]([C:4]1[CH:27]=[CH:26][C:7]2[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH:12]=3)[CH:9]=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 223301115-Acetyl-1-(3-(1-acetylpiperazin-4-yl)phenyl)benzimidazole

Product 1

HCID 22330121HCID 22330121, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

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 5f, (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-897dcf1fa62d427fa7ad47a86b160b88
Source dataset
uspto-grants-2004_03
Patent number
US06710044B2

Reaction notes

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