Triethylamine → HCID 73051967, compound

HRID 1048706Notes

Reaction equation

HRID 1048706 reaction equation
I[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[CH2:11][N:12]([CH3:18])[CH2:13][C:14]([O:16][CH3:17])=[O:15].[F:19][C:20]([F:30])([F:29])[C:21]1[CH:22]=[C:23]([C:27]#[CH:28])[CH:24]=[CH:25][CH:26]=1.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=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]>[CH3:18][N:12]([CH2:11][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]2[C:2]=1[C:28]#[C:27][C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([C:20]([F:19])([F:29])[F:30])[CH:22]=1)[CH2:13][C:14]([O:16][CH3:17])=[O:15]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 27784901-Ethynyl-3-(trifluoromethyl)benzeneHCID 118195178HCID 118195178, compound

Product 1

HCID 73051967HCID 73051967, compoundYield 58.8%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a flask placed under an argon flow, 0.093 g (0.212 mmol) of methyl 2-(((3-iodoimidazo[1,2-a]pyridin-2-yl)methyl)(methyl)amino)acetate were dissolved in 0.5 ml of dimethylformamide with magnetic stirring. To this solution, were added: 0.004 g (0.021 mmol) of copper iodide, 0.037 ml (0.255 mmol) of 3-trifluoromethylphenylacetylene and 0.444 ml (3.18 mmol) of triethylamine. The reaction medium was degassed with argon for 10 min before adding 0.019 g (0.021 mmol) of Pd2(dba)3. The mixture was stirred at r.t. for 16 h before being treated, diluted with 15 ml of ethyl acetate and washed with 2×15 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 20 ml of ethyl acetate. The combined organic phases were dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: ethyl acetate 100%). 0.05 g (yield=57%) of methyl 2-(methyl((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methyl)amino)acetate were obtained as a pale brown solid. LC-MS: m/z=402 (MH+); UV purity at 254 nm=96%. 1H NMR (300 MHz, DMSO) δ 8.75 (d, J=6.7 Hz, 1H), 8.11 (s, 1H), 7.97 (d, J=7.6 Hz, 1H), 7.83-7.59 (m, 3H), 7.55-7.37 (m, 1H), 7.14 (td, J=6.8, 0.9 Hz, 1H), 3.97 (s, 2H), 3.58 (s, 3H), 3.43 (s, 2H), 2.39 (s, 3H).

Workup

  1. customIn a flask placed under an argon
  2. additionTo this solution, were added
  3. customThe reaction medium was degassed with argon for 10 min
  4. additionbefore being treated
  5. washwashed with 2×15 ml of a saturated NaCl aqueous solution
  6. extractionThe aqueous phase was extracted with 20 ml of ethyl acetate
  7. customThe combined organic phases were dried on Na2SO4 which
  8. customwas then removed by filtration
  9. concentrationThe obtained filtrate was concentrated in vacuo
  10. customThe crude residue was purified by flash chromatography on a silica gel cartridge (eluent: ethyl acetate 100%)

Sources & evidence

ORD record
ord-5e39c192047c4a43b4414f58ea03cd53
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

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