Potassium Carbonate → 6-tert-butyl-2-{3-[5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one

HRID 449628Notes

Reaction equation

HRID 449628 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=3)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:28]1[N:37]=[CH:36][C:35]2[C:30](=[C:31]([F:42])[CH:32]=[C:33]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:34]=2)[C:29]1=[O:43])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[C:38]([C:33]1[CH:34]=[C:35]2[C:30](=[C:31]([F:42])[CH:32]=1)[C:29](=[O:43])[N:28]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=4)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:37]=[CH:36]2)([CH3:41])([CH3:39])[CH3:40]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 667431562-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Product 1

HCID 566558106-tert-butyl-2-{3-[5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-oneYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

To 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (186 mg, 318 μmol, Eq: 1.00) in MeOH (15.0 ml) was added potassium carbonate (87.8 mg, 635 μmol, Eq: 2.0). The reaction mixture stirred at 40° C. for 2 h. The solution was cooled to room temperature. Concentrated in vacuo. The residue was taken up in DCM/water. The layers were separated. The aqueous layer was extracted once with DCM. The organic layers were combined, and then dried over Na2SO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 35% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-tert-butyl-2-{3-[5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one (75 mg, 44%). LC/MS-ESI observed [M+H]+ 544. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.43 (s, 9H) 2.28 (s, 3H) 3.75 (s, 3H) 3.88 (s, 3H) 4.40 (s, 2H) 5.92 (s, 1H) 7.41-7.60 (m, 4H) 7.62-7.69 (m, 1H) 7.78 (s, 1H) 7.96 (s, 1H) 8.29 (d, J=2.64 Hz, 1H)

Workup

  1. temperatureThe solution was cooled to room temperature
  2. concentrationConcentrated in vacuo
  3. customThe layers were separated
  4. extractionThe aqueous layer was extracted once with DCM
  5. dry with materialdried over Na2SO4
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 35% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)

Sources & evidence

ORD record
ord-8bd7c298ccdb40239a59a215cd5ae389
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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