1H-Pyrazol-3-amine, 5-methyl- → 2-Isopropyl-4-(5-methyl-1H-pyrazol-3-ylamino)-7-(2-methylsulfanyl-ethoxy)-2H-phthalazin-1-one

HRID 1783712Notes

Reaction equation

Br[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH2:13][CH2:14][S:15][CH3:16])=[CH:9][CH:10]=2)[C:5](=[O:17])[N:4]([CH:18]([CH3:20])[CH3:19])[N:3]=1.CC(C)([O-])C.[Na+].[NH2:27][C:28]1[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>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].C(OCC)C>[CH:18]([N:4]1[N:3]=[C:2]([NH:27][C:28]2[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=2)[C:11]2[C:6](=[CH:7][C:8]([O:12][CH2:13][CH2:14][S:15][CH3:16])=[CH:9][CH:10]=2)[C:5]1=[O:17])([CH3:20])[CH3:19]

Participants

Conditions

Temperature: 100 °C

Procedure

Degassed toluene (6 ml) and EtOH (3 ml) were added in one portion to a mixture of 4-bromo-2-isopropyl-7-(2-methylsulfanyl-ethoxy)-2H-phthalazin-1-one (0.3 g, 0.8 mmol), sodium t-butoxide (0.112 g, 1.2 mmol), 3-amino-5-methyl pyrazole (0.107 g, 1.2 mmol), tris-(dibenzylideneacetone)-dipalladium (0.038 g, 0.042 mmol) and 2-(di-t-butylphosphino)-biphenyl (0.025 g, 0.084 mmol) under nitrogen. The reaction mixture was heated to 100° C. for 20 hours with stirring and then cooled to RT. Diethyl ether (10 ml) was added and the precipitated solid was filtered to give the crude product as a grey solid. Flash column chromatography (elution: 95% EtOAc, 5% MeOH) afforded the title compound as a white solid (0.070 g, 7% yield).

Workup

customDegassed toluene (6 ml) and EtOH (3 ml)
temperaturecooled to RT
filtrationthe precipitated solid was filtered
customto give the crude product as a grey solid
washFlash column chromatography (elution: 95% EtOAc, 5% MeOH)

Sources & evidence

ORD record: ord-be436706b01948fcb9adab5d833f4aae
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07501410B2

Reaction notes

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