Dimethyl Sulfoxide → 2-fluoro-4-(3-(1-(6-fluoroquinolin-2-yl)piperidin-4-yl)pyrazin-2-yl)-N-methylbenzamide

HRID 624518노트

반응식

HRID 624518 반응식
[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:17]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[N:16][CH:15]=[CH:14][N:13]=2)[CH:9]=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].Cl[C:25]1[CH:34]=[CH:33][C:32]2[C:27](=[CH:28][CH:29]=[C:30]([F:35])[CH:31]=2)[N:26]=1.CS(C)=O.C(=O)([O-])[O-].[K+].[K+]>O.C(OCC)C>[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:17]([CH:18]3[CH2:23][CH2:22][N:21]([C:25]4[CH:34]=[CH:33][C:32]5[C:27](=[CH:28][CH:29]=[C:30]([F:35])[CH:31]=5)[N:26]=4)[CH2:20][CH2:19]3)=[N:16][CH:15]=[CH:14][N:13]=2)[CH:9]=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5]

참가 물질

7

반응물 4

HCID 679Dimethyl Sulfoxide2회HCID 11430Potassium CarbonateHCID 150594332-Chloro-6-fluoroquinolineHCID 867054042-fluoro-N-methyl-4-(3-(piperidin-4-yl)pyrazin-2-yl)benzamide

생성물 1

HCID 727147562-fluoro-4-(3-(1-(6-fluoroquinolin-2-yl)piperidin-4-yl)pyrazin-2-yl)-N-methylbenzamide수율 39.8%

시약·촉매·용매 2

HCID 962Water용매HCID 3283Diethyl Ether용매

반응 조건

온도
100 °C

실험 절차

To a solution of 2-fluoro-N-methyl-4-(3-(piperidin-4-yl)pyrazin-2-yl)benzamide (155 mg, 0.493 mmol, prepared according to Step 2 of Example 1), 2-chloro-6-fluoroquinoline (108 mg, 0.595 mmol, Combi-blocks), and DMSO (2 mL) was added potassium carbonate (240 mg, 1.737 mmol). The solution was stirred at 100° C. After 72 h, the reaction was allowed to cool to room temperature and diluted with water (50 mL). After stirring for 30 min, the solution was filtered and the filtered solid adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 0-80% EtOAc in hexane, to provide a light yellow solid, which contained residual DMSO as measure by NMR. The solids were redissolved in diethyl ether and washed with water, brine, and concentrated in vacuo to give 2-fluoro-4-(3-(1-(6-fluoroquinolin-2-yl)piperidin-4-yl)pyrazin-2-yl)-N-methylbenzamide (90 mg, 0.196 mmol, 39.7% yield), as a light yellow solid. m/z=460 (M+1). 1H NMR (300 MHz, CDCl3) δ ppm 8.55 (d, J=2.48 Hz, 1H), 8.49 (d, J=2.48 Hz, 1H), 8.26 (t, J=8.04 Hz, 1H), 7.82 (d, J=9.21 Hz, 1H), 7.65 (dd, J=5.26, 9.06 Hz, 1H), 7.44 (dd, J=1.61, 8.04 Hz, 1H), 7.36 (dd, J=1.61, 12.42 Hz, 1H), 7.28-7.32 (m, 1H), 7.22 (dd, J=2.92, 8.92 Hz, 1H), 7.04 (d, J=9.21 Hz, 1H), 6.77 (br. s., 1H), 4.64 (d, J=13.45 Hz, 2H), 3.14-3.31 (m, 1H), 3.03-3.14 (m, 3H), 2.81-3.02 (m, 2H), 2.05-2.21 (m, 2H), 1.82 (d, J=11.69 Hz, 2H).

후처리

  1. temperatureto cool to room temperature
  2. stirringAfter stirring for 30 min
  3. filtrationthe solution was filtered
  4. customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
  5. washeluting with 0-80% EtOAc in hexane
  6. customto provide a light yellow solid, which
  7. washwashed with water, brine
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-edf866324f72447cb84fe79012fe4793
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303028B2

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