4-[(Piperazin-1-yl)methyl]benzonitrile → 4-((4-(8-Methyl-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperazin-1-yl)methyl)benzonitrile

HRID 1674776Notes

Reaction equation

[C:1]([C:3]1[CH:15]=[CH:14][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:5][CH:4]=1)#[N:2].Cl[C:17]1[CH:18]=[C:19]([CH3:30])[C:20]2[N:21]([C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=2)[N:22]=1>C(O)C>[CH3:30][C:19]1[C:20]2[N:21]([C:23]([C:26]([F:29])([F:27])[F:28])=[N:24][N:25]=2)[N:22]=[C:17]([N:11]2[CH2:12][CH2:13][N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:15][CH:14]=3)[CH2:9][CH2:10]2)[CH:18]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 1-(4-cyanobenzyl)-piperazine (0.158 g, 0.79 mmol) and 6-chloro-8-methyl-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine 0.062 g, 0.26 mmol) in ethanol (5 mL) was heated to 70° C. for 20 hours. The reaction mixture was allowed to cool and then concentrated to give an involatile residue that was purified by flash chromatography on silica-gel using an increasing gradient of ethyl acetate in dichloromethane to give 4-((4-(8-methyl-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperazin-1-yl)methyl)benzonitrile (0.0676 g, 64.3%) as a white solid; 1H NMR spectrum (CDCl3) δ 2.47-2.55 (4H, m), 2.61 (3H, d), 3.50-3.60 (6H, m), 6.72-6.76 (1H, m), 7.42 (2H, d), 7.57 (2H, d); m/z 402.69 (M+1)+.

Workup

temperatureto cool
concentrationconcentrated
customto give an involatile residue that
customwas purified by flash chromatography on silica-gel

Sources & evidence

ORD record: ord-3bae5157dd204f6fb7770347bcf4ba30
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003649B2

Reaction notes

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