Sodium Carbonate → 4-[(3-Chloro-4-methoxybenzyl)amino]-1-[4-(methoxyimino)piperidino]-6-phthalazine carbonitrile

HRID 47348Notes

Reaction equation

HRID 47348 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:5][NH:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[N:18])[CH:15]=2)[C:10]([N:19]2[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]2)=[N:9][N:8]=1.Cl.[CH3:32][O:33][NH2:34].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:5][NH:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[N:18])[CH:15]=2)[C:10]([N:19]2[CH2:20][CH2:21][C:22](=[N:34][O:33][CH3:32])[CH2:23][CH2:24]2)=[N:9][N:8]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 521874O-Methylhydroxylamine hydrochlorideHCID 105040684-(3-Chloro-4-methoxy-benzylamino)-1-(4-oxo-piperidin-1-yl)-phthalazine-6-carbonitrile; hydrochloride

Product 1

HCID 227444584-[(3-Chloro-4-methoxybenzyl)amino]-1-[4-(methoxyimino)piperidino]-6-phthalazine carbonitrileYield 48.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1.19 g 4-[(3-chloro-4-methoxybenzyl)amino]-1-[4-oxopiperidino]-6-phthalazine carbonitrile, 354 mg methoxyamine hydrochloride, 1.2 g sodium carbonate, and 10 ml ethanol was heated under reflux for 2 hr. After cooling, saline was added to the reaction solution which was then extracted with ethyl acetate. It was dried over anhydrous sodium sulfate, and filtered. The filtrate was evaporated, and the resulting residue was purified by silica gel column chromatography to give 620 mg of 4-[(3-chloro-4-methoxybenzyl)amino]-1-[4-(methoxyimino)piperidino]-6-phthalazine carbonitrile. This product was dissolved in a mixed solvent of methanol and ethanol, and recrystallized by adding 0.35 ml of 4 N hydrochloric acid/ethyl acetate to give 388 mg of 4-[(3-chloro-4-methoxybenzyl)amino]-1-[4-(methoxyimino)piperidino]-6-phthalazinecarbonitrile hydrochloride.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hr
  3. temperatureAfter cooling
  4. additionsaline was added to the reaction solution which
  5. extractionwas then extracted with ethyl acetate
  6. dry with materialIt was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customThe filtrate was evaporated
  9. customthe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fe397180f11f4113be6e005dcd113628
Source dataset
uspto-grants-2004_03
Patent number
US06699870B2

Reaction notes

Loading…