Water → HCID 24753772, compound

HRID 1783729Notes

Reaction equation

HRID 1783729 reaction equation
[CH:1]([N:4]1[N:13]=[C:12]([NH:14][C:15]2[CH:19]=[C:18]([CH3:20])[NH:17][N:16]=2)[C:11]2[C:6](=[CH:7][C:8]([NH:21][CH3:22])=[CH:9][CH:10]=2)[C:5]1=[O:23])([CH3:3])[CH3:2].[H-].[Na+].[CH3:26][O:27][CH2:28][C:29](Cl)=[O:30].O>CN(C=O)C>[CH:1]([N:4]1[C:5](=[O:23])[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([N:21]([CH3:22])[C:29](=[O:30])[CH2:28][O:27][CH3:26])[CH:7]=2)[C:12]([NH:14][C:15]2[CH:19]=[C:18]([CH3:20])[NH:17][N:16]=2)=[N:13]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 96623Methoxyacetyl chlorideHCID 21106483HCID 21106483, compound

Product 1

HCID 24753772HCID 24753772, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2-Isopropyl-7-methylamino-4-(5-methyl-1H-pyrazol-3-ylamino)-2H-phthalazin-1-one (0.4 g, 1.3 mmol) was dissolved in DMF (5 ml). To this was added NaH (60%, 0.1 g, 2.6 mmol) as a suspension in DMF (2 ml). The mixture was stirred at RT for 5 min then methoxyacetyl chloride (0.28 g, 2.6 mmol) was added dropwise and the reaction mixture was stirred at RT for 2 hours. After this time, water (10 ml) was added cautiously, the mixture was extracted with EtOAc (3×10 ml), the organic layers were combined, dried (MgSO4), filtered and concentrated under vacuum. The residue was dissolved in THF (5 ml) and heated to 60° C. in the presence of solid sodium hydroxide (100 mg) for 2 hours. After this time the mixture was concentrated under vacuum and subjected to flash column chromatography (elution: 95% EtOAc, 5% MeOH) to give N-[3-isopropyl-1-(5-methyl-1H-pyrazol-3-ylamino)-4-oxo-3,4-dihydro-phthalazin-6-yl]-2-methoxy-N-methyl-acetamide (0.06 g, 12% yield) as a white solid.

Workup

  1. stirringthe reaction mixture was stirred at RT for 2 hours
  2. extractionthe mixture was extracted with EtOAc (3×10 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. dissolutionThe residue was dissolved in THF (5 ml)
  7. temperatureheated to 60° C. in the presence of solid sodium hydroxide (100 mg) for 2 hours
  8. concentrationAfter this time the mixture was concentrated under vacuum
  9. washsubjected to flash column chromatography (elution: 95% EtOAc, 5% MeOH)

Sources & evidence

ORD record
ord-089f47a9731b451f9cd7725d9a53b8a5
Source dataset
uspto-grants-2009_03
Patent number
US07501410B2

Reaction notes

Loading…