Hydrochloric Acid → 2-Quinolinecarboxamide

HRID 922786노트

반응식

HRID 922786 반응식
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]

참가 물질

4

반응물 3

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

생성물 1

HCID 1457872-Quinolinecarboxamide

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d8ebda9cee66405f85edab4ba7faaed2
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278960B2

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