Hydrochloric Acid → 2-Quinolinecarboxamide

HRID 922786ノート

反応式

HRID 922786 の反応式
FC1C=CC([C:8]2[C:17]3[C:12](=[CH:13][C:14](CN4CC(C(F)(F)F)NC[C@@H]4C)=[CH:15][CH:16]=3)[N:11]=[C:10]([C:30]#[N:31])[CH:9]=2)=CC=1.Cl.C(=O)([O-])[O-:34].[K+].[K+]>>[N:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:8]=[CH:9][C:10]=1[C:30]([NH2:31])=[O:34]

参加物

4

反応物 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 895548164-(4-fluorophenyl)-7-(((2S)-2-methyl-5-(trifluoromethyl)piperazin-1-yl)methyl)quinoline-2-carbonitrile

生成物 1

HCID 1457872-Quinolinecarboxamide

実験手順

4-(4-fluorophenyl)-7-(((2S)-2-methyl-5-(trifluoromethyl)piperazin-1-yl)methyl)quinoline-2-carbonitrile (275 mg, 0.642 mmol) was dissolved in conc HCl (2636 μl, 32.1 mmol) and then stirred at ambient temperature for 4 hours. The yellow solution was slowly poured into aq potassium carbonate (12.8 ml, 5M, 64 mmol) at 0° C. The resulting mixture was extracted with chloroform. The organic portion was dried over MgSO4 and concentrated. The residue was purified by preparative HPLC Chiralpak AD, 5 cm×500 cm, 50 ml/min eluting with 20% IPA/hexanes+0.1% Et□NH, to provide isomers A and B of 4-(4-fluorophenyl)-7-(((2S)-2-methyl-5(R or S)-(trifluoromethyl)piperazin-1-yl)methyl)quinoline-2-carboxamide as colorless foams. Isomer A, LRMS m/z (M+H)+ 447.3 found, 447.4 required 1H NMR (500 MHz, CDCl3): 8.22 (1H, s), 8.10 (2H, d, J=12.11 Hz), 7.91 (1H, d, J=8.69 Hz), 7.65 (1H, dd, J=8.72, 1.66 Hz), 7.52 (2H, dd, J=8.44, 5.36 Hz), 5.64 (1H, s), 3.89 (1H, d, J=13.93 Hz), 3.77 (1H, d, J=13.94 Hz), 3.39-3.34 (1H, m), 3.08-3.04 (1H, m), 2.94-2.87 (2H, m), 2.73 (1H, dd, J=11.54, 8.93 Hz), 2.60 (1H, dd, J=11.55, 3.62 Hz), 1.17 (3H, d, J=6.41 Hz).

後処理

  1. extractionThe resulting mixture was extracted with chloroform
  2. dry with materialThe organic portion was dried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC Chiralpak AD, 5 cm×500 cm, 50 ml/min
  5. washeluting with 20% IPA/hexanes+0.1% Et

出典と根拠

ORDレコード
ord-d8ebda9cee66405f85edab4ba7faaed2
出典データセット
uspto-grants-2016_03
特許番号
US09278960B2

反応ノート

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