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

HRID 58104노트

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HRID 58104 반응식
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

참가 물질

4

반응물 2

HCID 897832784-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazoleHCID 178514179HCID 178514179, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9283214c171f4497b34d58a0a846c17e
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434743B2

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