Acetonitrile → 4,5-Dimethyl-6-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyridazin-3-yl-acetonitrile

HRID 447133Notes

Reaction equation

Cl[C:2]1[N:3]=[N:4][C:5]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[C:6]([CH3:9])[C:7]=1[CH3:8].[C:26](#[N:28])[CH3:27].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1(C)C=CC=CC=1>[CH3:8][C:7]1[C:6]([CH3:9])=[C:5]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=3)[CH2:12][CH2:11]2)[N:4]=[N:3][C:2]=1[CH2:27][C:26]#[N:28]

Participants

Conditions

Temperature: 0 °C

Procedure

3-Chloro-4,5-dimethyl-6-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyridazine (1.0 g, 2.64 mmol), acetonitrile (0.225 mL, 4.22 mmol), and toluene (5 mL) are combined and cooled to 0° C. LiHMDS (8.4 mL, 1.0 M, 8.4 mmol) is added dropwise over 5 min. The reaction is stirred at 0° C. for 1 h, then warmed to room temperature and stirred an additional 16 h. The reaction is quenched by the addition of saturated aq. NH4Cl, and the organics are extracted with EtOAc. The combined organic layers are dried over MgSO4 and concentrated. The residue is purified by flash chromatography on silica gel (0-100% EtOAc in heptanes) to afford the title compound as an orange solid (500 mg, 50%).

Workup

temperaturewarmed to room temperature
stirringstirred an additional 16 h
customThe reaction is quenched by the addition of saturated aq. NH4Cl
extractionthe organics are extracted with EtOAc
dry with materialThe combined organic layers are dried over MgSO4
concentrationconcentrated
customThe residue is purified by flash chromatography on silica gel (0-100% EtOAc in heptanes)

Sources & evidence

ORD record: ord-697d2ccb70404ccfb3ad17da839f0778
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481542B2

Reaction notes

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