Hydrochloric Acid → 2-Quinolinecarboxamide

HRID 922786Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 922786
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]

Komponenten

4

Edukt 3

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

Produkt 1

HCID 1457872-Quinolinecarboxamide

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-d8ebda9cee66405f85edab4ba7faaed2
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278960B2

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