Dimethylacetamide → 4-(4-fluorophenyl)-7-(((2S)-2-methyl-5-(trifluoromethyl)piperazin-1-yl)methyl)quinoline-2-carbonitrile

HRID 922785Notes

Reaction equation

[CH3:1][C@H:2]1[CH2:7][NH:6][CH:5]([C:8]([F:11])([F:10])[F:9])[CH2:4][NH:3]1.CC(N(C)C)=O.CCN(C(C)C)C(C)C.Br[CH2:28][C:29]1[CH:38]=[C:37]2[C:32]([C:33]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=3)=[CH:34][C:35]([C:39]#[N:40])=[N:36]2)=[CH:31][CH:30]=1>CCOC(C)=O>[F:47][C:44]1[CH:45]=[CH:46][C:41]([C:33]2[C:32]3[C:37](=[CH:38][C:29]([CH2:28][N:3]4[CH2:4][CH:5]([C:8]([F:11])([F:9])[F:10])[NH:6][CH2:7][C@@H:2]4[CH3:1])=[CH:30][CH:31]=3)[N:36]=[C:35]([C:39]#[N:40])[CH:34]=2)=[CH:42][CH:43]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To the solution of (2S)-2-methyl-5-(trifluoromethyl)piperazine (4-20) was added DMA (1.76 ml), DIEA (0.614 ml, 3.52 mmol) followed by 7-(bromomethyl)-4-(4-fluorophenyl)quinoline-2-carbonitrile (300 mg, 0.879 mmol). The reaction was heated to 50° C. for 4 hours. The reaction was diluted with EtOAc and then washed with H2O, brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica gel eluting with hexanes to EtOAc to provide 4-(4-fluorophenyl)-7-(((2S)-2-methyl-5-(trifluoromethyl)piperazin-1-yl)methyl)quinoline-2-carbonitrile as a colorless solid. LRMS m/z (M+H)+ 429.2 found, 429.4 required.

Workup

washwashed with H2O, brine
dry with materialdried (MgSO4)
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel eluting with hexanes to EtOAc

Sources & evidence

ORD record: ord-e5c5b617b3e14df39dfe813d851feac0
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278960B2

Reaction notes

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