Nitrogen → N1-Benzyl-N2-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)ethane-1,2-diamine

HRID 2093362Notes

Reaction equation

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

Participants

Conditions

Temperature: 95 °C

Procedure

Treat a N2 degassed mixture of N1-benzyl-N2-(6-chloro-4,5-dimethylpyridazin-3-yl)ethane-1,2-diamine (6.40 g, 22.0 mmol), 4-fluorophenylboronic acid (9.24 g, 66.0 mmol) and CsF (10.0 g, 66.0 mmol) in 1,4-dioxane (220 mL) with (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) chloride (2.70 g, 3.30 mmol). Heat the reaction mixture at 95° C. overnight. Cool, and partition between saturated NaHCO3 (aq) and EtOAc. Separate the layers, and extract the aqueous layer with EtOAc. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 6% 2M NH3/MeOH in CH2Cl2) to afford the title compound as a waxy solid (4.91 g, 64%). ES/MS m/z 351.2 (M+1).

Workup

customdegassed
temperatureCool
custompartition between saturated NaHCO3 (aq) and EtOAc
customSeparate the layers
extractionextract the aqueous layer with EtOAc
dry with materialdry over Na2SO4
filtrationfilter
concentrationconcentrate under reduced pressure
customPurify the residue by flash silica gel chromatography (gradient of 0 to 6% 2M NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-3a4377fc7b5341cfb00f9c15ece34c03
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445493B2

Reaction notes

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