Hydroxyamine hydrochloride → HCID 178509529, compound

HRID 2110022Notes

Reaction equation

HRID 2110022 reaction equation
[C:1]1([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([CH2:18][NH:19][C:20]3[NH:24][C:23]4[CH:25]=[CH:26][C:27]([CH:29]=O)=[CH:28][C:22]=4[N:21]=3)[CH2:14][CH2:13]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH2:32]O.Cl.O1CCOCC1>CN(C)C=O.Cl.[OH-].[Na+]>[C:1]1([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([CH2:18][NH:19][C:20]3[NH:24][C:23]4[CH:25]=[CH:26][C:27]([C:29]#[N:32])=[CH:28][C:22]=4[N:21]=3)[CH2:14][CH2:13]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 204431481,4-Dioxane hydrochlorideHCID 178519373HCID 178519373, compound

Product 1

HCID 178509529HCID 178509529, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 14798Sodium HydroxideCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

After dissolving 2-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-amino]-1H-benzimidazole-5-carboaldehyde (2.7 mg, 0.0570 mmol) in anhydrous dimethylformamide (1 ml) under a nitrogen stream, hydroxylamine hydrochloride (8 mg, 0.115 mmol) and one drop of 6N hydrochloric acid were added and the mixture was stirred at 80° C. for 2 hours and 30 minutes. Two drops of 5N aqueous sodium hydroxide were then added, and after extraction with ethyl acetate, extraction was repeated with dichloromethane. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a residue. Anhydrous dimethylformamide (1 ml) and nine drops of a 4N hydrogen chloride/1,4-dioxane solution were added to the residue, and the mixture was stirred at 100° C. for 12 hours. After neutralization with 5N aqueous sodium hydroxide, the same extraction procedure was carried out and the obtained residue was purified by thin-layer silica gel chromatography (dichloromethane/methanol/triethylamine=85/10/5) to obtain 2-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-amino]-1H-benzimidazole-5-carbonitrile.

Workup

  1. additionwere added
  2. extractionafter extraction
  3. extractionwith ethyl acetate, extraction
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customto obtain a residue
  8. stirringthe mixture was stirred at 100° C. for 12 hours
  9. extractionAfter neutralization with 5N aqueous sodium hydroxide, the same extraction procedure
  10. customthe obtained residue was purified by thin-layer silica gel chromatography (dichloromethane/methanol/triethylamine=85/10/5)

Sources & evidence

ORD record
ord-739a83ec68fc4d12a49bbc7622522252
Source dataset
uspto-grants-2009_04
Patent number
US07517875B2

Reaction notes

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