Triethylamine → 2-Fluoro-4-(3-(1-(7-fluoroquinolin-2-YL)piperidin-4-YL)pyrazin-2-YL)-N-methylbenzamide

HRID 2364573ノート

反応式

HRID 2364573 の反応式
Cl.Cl.Cl.[F:4][C:5]1[CH:14]=[C:13]([C:15]2[C:20]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[N:19][CH:18]=[CH:17][N:16]=2)[CH:12]=[CH:11][C:6]=1[C:7]([NH:9][CH3:10])=[O:8].C(N(CC)CC)C.FC(F)(F)S(O[C:40]1[CH:49]=[CH:48][C:47]2[C:42](=[CH:43][C:44]([F:50])=[CH:45][CH:46]=2)[N:41]=1)(=O)=O>CS(C)=O.O>[F:4][C:5]1[CH:14]=[C:13]([C:15]2[C:20]([CH:21]3[CH2:26][CH2:25][N:24]([C:40]4[CH:49]=[CH:48][C:47]5[C:42](=[CH:43][C:44]([F:50])=[CH:45][CH:46]=5)[N:41]=4)[CH2:23][CH2:22]3)=[N:19][CH:18]=[CH:17][N:16]=2)[CH:12]=[CH:11][C:6]=1[C:7]([NH:9][CH3:10])=[O:8]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 866941337-Fluoroquinolin-2-yl trifluoromethanesulfonateHCID 867054032-fluoro-N-methyl-4-(3-(piperidin-4-yl)pyrazin-2-yl)benzamide trihydrochloride

生成物 1

HCID 727147542-Fluoro-4-(3-(1-(7-fluoroquinolin-2-YL)piperidin-4-YL)pyrazin-2-YL)-N-methylbenzamide収率 46.1%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 962Water溶媒

反応条件

温度
60 °C

実験手順

To a RT solution of 2-fluoro-N-methyl-4-(3-(piperidin-4-yl)pyrazin-2-yl)benzamide trihydrochloride (1.00 g, 3.18 mmol, prepared according to Step 2 of Example 1) and triethylamine (2.00 ml, 14.35 mmol) in DMSO (10 ml) was added a solution of 7-fluoroquinolin-2-yl trifluoromethanesulfonate (1.10 g, 3.73 mmol, prepared according to Step 3 of Example 2) in DMSO (2 mL). The reaction mixture was heated at 60° C. for 2.5 h. The reaction was cooled RT and diluted with water. The mixture was extracted with CH2Cl2 (3×). The combined organic layers were washed with brine and dried over Na2SO4. The solution was filtered and the solution was evaporated onto silica gel and purified by flash chromatography (Isco (80 gram)) eluting with EtOAc:hexanes (0:1→3:1). The fractions containing product were concentrated in vacuo and the residue was stirred vigorously over Et2O for 3 h. The solid was filtered, washed with Et2O and dried to give 674 mg (46%) of the desired product. m/z=460 (M+1). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.62 (d, J=2.34 Hz, 1H), 8.59 (d, J=2.34 Hz, 1H), 8.39 (br. s., 1H), 8.04 (d, J=9.21 Hz, 1H), 7.69-7.83 (m, 2H), 7.45-7.58 (m, 2H), 7.18-7.28 (m, 2H), 7.08 (td, J=8.77, 2.63 Hz, 1H), 4.66 (d, J=13.30 Hz, 2H), 3.13-3.29 (m, 1H), 2.86-3.03 (m, 2H), 2.82 (d, J=4.68 Hz, 3H), 1.72-1.97 (m, 4H).

後処理

  1. temperatureThe reaction was cooled RT
  2. extractionThe mixture was extracted with CH2Cl2 (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered
  6. customthe solution was evaporated onto silica gel
  7. custompurified by flash chromatography (Isco (80 gram))
  8. washeluting with EtOAc:hexanes (0:1→3:1)
  9. additionThe fractions containing product
  10. concentrationwere concentrated in vacuo
  11. filtrationThe solid was filtered
  12. washwashed with Et2O
  13. customdried

出典と根拠

ORDレコード
ord-536b98e0d57f457d9d61489d61c127a9
出典データセット
uspto-grants-2014_04
特許番号
US08691986B2

反応ノート

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