Triethylamine → 1-(cyclopropylmethyl)-5-(pyridin-3-ylethynyl)-4-(trifluoromethyl)-1H-benzotriazole

HRID 1618939Notes

Reaction equation

HRID 1618939 reaction equation
FC(F)(F)S(O[C:7]1[CH:19]=[CH:18][C:10]2[N:11]([CH2:14][CH:15]3[CH2:17][CH2:16]3)[N:12]=[N:13][C:9]=2[C:8]=1[C:20]([F:23])([F:22])[F:21])(=O)=O.[C:26]([C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1)#[CH:27].C(N(CC)CC)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:15]1([CH2:14][N:11]2[C:10]3[CH:18]=[CH:19][C:7]([C:27]#[C:26][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[C:8]([C:20]([F:23])([F:22])[F:21])[C:9]=3[N:13]=[N:12]2)[CH2:17][CH2:16]1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 1860033-EthynylpyridineHCID 867119761-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl trifluoromethanesulfonate

Product 1

HCID 710028481-(cyclopropylmethyl)-5-(pyridin-3-ylethynyl)-4-(trifluoromethyl)-1H-benzotriazole

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

1-(Cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl trifluoromethanesulfonate (25 mg, 0.064 mmol), 3-ethynylpyridine (13.3 mg, 0.128 mmol), triethylamine (116 μL, 0.835 mmol), tetra-n-butyl ammonium iodide (0.1 equiv), and copper (I) iodide (4 mg, 0.019 mmol) were combined in DMF (0.64 mL) and the mixture was sparged under nitrogen. Tetrakis(triphenylphosphine) palladium (0) (7.4 mg, 0.0064 mmol) was added, the mixture was sparged under nitrogen and then heated at 90° C. for 18 hours. The mixture was cooled to ambient temperature, diluted with ethyl acetate and washed with water and brine. The organic extract was dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (0-55% EtOAc in hexanes), providing the titled compound as a light yellow solid: 1H-NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 8.61 (dd, J=4.9, 1.7 Hz, 1H), 7.87 (dt, J=7.9, 2.0 Hz, 1H), 7.76 (s, 2H), 7.34 (dd, J=7.9, 4.9 Hz, 1H), 4.58 (d, J=7.2 Hz, 2H), 1.41 (m, 1H), 0.66-0.73 (m, 2H), 0.51-0.55 (m, 2H) ppm; LRMS (ES+) m/z 343.1 [(M+H)+; calculated for C18H14F3N4: 343.2].

Workup

  1. customthe mixture was sparged under nitrogen
  2. customthe mixture was sparged under nitrogen
  3. temperatureThe mixture was cooled to ambient temperature
  4. additiondiluted with ethyl acetate
  5. washwashed with water and brine
  6. extractionThe organic extract
  7. dry with materialwas dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel gradient chromatography (0-55% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c7374261a4db4d9ab77b9387d2d59352
Source dataset
uspto-grants-2014_07
Patent number
US08772276B2

Reaction notes

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