Cesium carbonate → 6-Bromo-4-(2-tert-butyl-5-methyl-2H-pyrazol-3-ylamino)-2-(4-tert-butyl-phenyl)-2H-phthalazin-1-one

HRID 1765392Notes

Reaction equation

HRID 1765392 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Br:12])[CH:10]=2)[C:5](=[O:13])[N:4]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[N:3]=1.[C:24]([N:28]1[C:32]([NH2:33])=[CH:31][C:30]([CH3:34])=[N:29]1)([CH3:27])([CH3:26])[CH3:25].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[C:5](=[O:13])[N:4]([C:14]1[CH:19]=[CH:18][C:17]([C:20]([CH3:22])([CH3:23])[CH3:21])=[CH:16][CH:15]=1)[N:3]=[C:2]2[NH:33][C:32]1[N:28]([C:24]([CH3:27])([CH3:26])[CH3:25])[N:29]=[C:30]([CH3:34])[CH:31]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7372001-tert-Butyl-3-methyl-1H-pyrazol-5-amineHCID 21106542HCID 21106542, compound

Product 1

HCID 211065786-Bromo-4-(2-tert-butyl-5-methyl-2H-pyrazol-3-ylamino)-2-(4-tert-butyl-phenyl)-2H-phthalazin-1-oneYield 194.9%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

11 mg 4,6-Dibromo-2-(4-tert-butyl-phenyl)-2H-phthalazin-1-one (preparation see ZA-1) were reacted with 39.0 mg 1-tert.-butyl-3-methyl-1H-pyrazol-5-ylamine, 132 mg cesium carbonate, 7.0 mg tris-(dibenzylideneacetone)-dipalladium and 8.8 mg 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene were stirred under argon at 100° C. for 20 hrs until HPLC indicated complete conversion. The solvent was removed under vacuum, the residue was taken up in dichloromethane and washed dilute HCl. Removal of the dichloromethane and chromatography on silica in first heptane and then heptan/ethyl acetate 8:2 yielded 25 mg of the title product.

Workup

  1. customThe solvent was removed under vacuum
  2. washwashed dilute HCl
  3. customRemoval of the dichloromethane and chromatography on silica in first heptane

Sources & evidence

ORD record
ord-8f2513b0cdab450e928774948b5a21ac
Source dataset
uspto-grants-2007_06
Patent number
US07226923B2

Reaction notes

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