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

HRID 58104Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-9283214c171f4497b34d58a0a846c17e
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434743B2

Reaction notes

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