Cesium fluoride → HCID 58379008, compound

HRID 1951162Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@@H:14]([CH3:25])[CH2:13]2)=[N:4][N:3]=1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.[F-].[Cs+]>O1CCOCC1>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([N:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@@H:14]([CH3:25])[CH2:13]3)=[N:4][N:3]=2)=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 95 °C

Procedure

Treat a degassed mixture of (S)-tert-butyl 4-(4-chlorophthalazin-1-yl)-2-methylpiperazine-1-carboxylate (0.81 g, 2.23 mmol), 4-methoxybenzeneboronic acid (1.07 g, 7.05 mmol) and cesium fluoride (1.05 g, 6.94 mmol) in 1,4-dioxane (30 mL) with (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) chloride (0.27 g, 0.33 mmol). Heat the resulting mixture at 95° C. overnight. Partition the reaction mixture between water and EtOAc. Extract the aqueous layer with EtOAc. Wash the organic portion with water and brine, dry over Na2SO4, and concentrate under reduced pressure. Purify the resulting residue by flash silica gel chromatography (gradient of 15 to 70% EtOAc in hexanes) to provide the title compound (0.94 g, 96%). ES/MS m/z 435.2 (M+1).

Workup

additionTreat
customPartition the reaction mixture between water and EtOAc
extractionExtract the aqueous layer with EtOAc
washWash the organic portion with water and brine
dry with materialdry over Na2SO4
concentrationconcentrate under reduced pressure
customPurify the resulting residue by flash silica gel chromatography (gradient of 15 to 70% EtOAc in hexanes)

Sources & evidence

ORD record: ord-23a57a7760e64b5abb70e5e9de3b295e
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404687B2

Reaction notes

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