Nitrogen → (S)-tert-Butyl 4-(4,5-dimethyl-6-phenylpyridazin-3-yl)-2-methylpiperazine-1-carboxylate

HRID 2093359Notes

Reaction equation

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

Participants

Conditions

Temperature: 95 °C

Procedure

Treat a N2 degassed mixture of (S)-tert-butyl 4-(6-chloro-4,5-dimethylpyridazin-3-yl)-2-methylpiperazine-1-carboxylate (3.03 g, 8.87 mmol), phenylboronic acid (1.62 g, 13.3 mmol), and CsF (4.09 g, 26.9 mmol) in 1,4-dioxane (120 mL) with (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) chloride (1.08 g, 1.32 mmol). Heat the reaction mixture at 95° C. overnight. Cool the reaction, and partition between EtOAc and H2O. Wash the organic layer with brine, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 15 to 85% EtOAc in hexanes) to afford the title compound as a white solid (2.93 g, 86%). ES/MS m/z 383.0 (M+1).

Workup

customdegassed
temperatureCool
customthe reaction
custompartition between EtOAc and H2O
washWash the organic layer with brine
dry with materialdry over Na2SO4
filtrationfilter
concentrationconcentrate under reduced pressure
customPurify the residue by flash silica gel chromatography (gradient of 15 to 85% EtOAc in hexanes)

Sources & evidence

ORD record: ord-02ab26925b524505a6e29cd6bc0292a9
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445493B2

Reaction notes

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