Triethylamine → HCID 73052445, compound

HRID 1048723Notes

Reaction equation

HRID 1048723 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](I)=[C:9]([CH2:11][S:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:10]=2)[CH:7]=1.[C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1)#[CH:21].C(N(CC)CC)C>CN(C=O)C.[Cu](I)I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:21]#[C:20][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:29])([F:30])[F:31])[CH:23]=3)=[C:9]([CH2:11][S:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:10]=2)[CH:7]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 27784901-Ethynyl-3-(trifluoromethyl)benzeneHCID 118195329HCID 118195329, compound

Product 1

HCID 73052445HCID 73052445, compoundYield 85.7%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

In an argon atmosphere, 27 g (59.8 mmol) of ethyl 2-((6-chloro-3-iodoimidazo[1,2-a]-pyridin-2-yl)methylthio)acetate, 9.51 ml (65.8 mmol) of 1-ethynyl-3-(trifluoromethyl)benzene, 1.139 g (5.98 mmol) of copper iodide and 125 ml (897 mmol) of triethylamine are loaded in 100 ml of DMF. Argon was bubbled in the solution for 10 min, and then 2.74 g (2.99 mmol) of Pd2(dba)3 were added. The mixture was stirred for 1 h at r.t. The catalyst was filtered on folded paper, the solution was poured onto 300 ml of water, extracted with 2×200 ml of ethyl acetate, the collected organic phases were washed with 3×150 ml of water and once with 150 ml of brine, dried on Na2SO4 which was then removed by filtration and the obtained filtrate was concentrated in vacuo. The residue was purified on a silica cake, and eluted with a heptane/ethyl acetate mixture. 23.21 g (yield=85%) of ethyl 2-((6-chloro-3-((3-(trifluoromethyl)phenyl)ethynyl)-imidazo[1,2-a]pyridin-2-yl)methylthio)acetate were obtained as a yellow solid. LC-MS: m/z=453 (MH+) UV purity at 254 nm=99%. 1H NMR (300 MHz, DMSO) δ 8.91 (dd, J=1.9, 0.6 Hz, 1H), 8.14 (s, 1H), 8.01 (d, J=7.6 Hz, 1H), 7.71 (ddd, J=14.3, 9.4, 4.3 Hz, 3H), 7.47 (dd, J=9.5, 2.0 Hz, 1H), 4.18-3.93 (m, 4H), 3.46 (s, 2H), 1.11 (t, J=7.1 Hz, 3H).

Workup

  1. customArgon was bubbled in the solution for 10 min
  2. filtrationThe catalyst was filtered on folded paper
  3. additionthe solution was poured onto 300 ml of water
  4. extractionextracted with 2×200 ml of ethyl acetate
  5. washthe collected organic phases were washed with 3×150 ml of water and once with 150 ml of brine
  6. customdried on Na2SO4 which
  7. customwas then removed by filtration
  8. concentrationthe obtained filtrate was concentrated in vacuo
  9. customThe residue was purified on a silica cake
  10. washeluted with a heptane/ethyl acetate mixture

Sources & evidence

ORD record
ord-e93c04c99f1341e983dcd583ebe0c241
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

Loading…