4-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole → 6-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinonitrile

HRID 58104ノート

反応式

HRID 58104 の反応式
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)=[CH:4][CH:3]=1.[C:22]([Zn]C#N)#[N:23]>CN(C=O)C>[CH3:8][C:6]1[N:7]=[C:2]([C:22]#[N:23])[CH:3]=[CH:4][C:5]=1[C:9]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]2[C:10]=1[CH:11]=[N:12][NH:13]2

参加物

4

反応物 2

HCID 897832784-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazoleHCID 178514179HCID 178514179、化合物

生成物 1

HCID 897829316-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinonitrile収率 34%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

A mixture of 4-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole (0.97 g, 3.11 mmol), dicyanozinc (1.462 g, 12.45 mmol), and tetrakis(triphenylphoshine)palladium(0) (0.360 g, 0.311 mmol) in DMF (15 mL) was thoroughly degassed by nitrogen and stirred at 120° C. for 24 hours. The reaction mixture was subsequently cooled and diluted with EtOAc then washed with brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by CombiFlash® chromatography, eluting with a gradient of 0-100% EtOAc in hexane. The product-containing fractions were combined and concentrated in vacuo to give the title compound as a white solid (0.32 g, 34%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.39 (s, 3H), 7.45 (d, J=1.01 Hz, 1H), 7.90-8.16 (m, 4H), 13.81 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C15H9F3N4, 303.1. found 303.18.

後処理

  1. customwas thoroughly degassed by nitrogen
  2. temperatureThe reaction mixture was subsequently cooled
  3. additiondiluted with EtOAc
  4. washthen washed with brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by CombiFlash® chromatography
  8. washeluting with a gradient of 0-100% EtOAc in hexane
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-9283214c171f4497b34d58a0a846c17e
出典データセット
uspto-grants-2016_09
特許番号
US09434743B2

反応ノート

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