Water → 2-((Pyridin-2-ylthio)methyl)-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo-[1,2-a]pyridine

HRID 1048730Notes

Reaction equation

HRID 1048730 reaction equation
Cl[CH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]2[C:11]=1[C:12]#[C:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[SH:30].C(=O)([O-])[O-].[Cs+].[Cs+].O>C(#N)C>[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[S:30][CH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]2[C:11]=1[C:12]#[C:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 90031792HCID 90031792, compoundHCID 178418616HCID 178418616, compound

Product 1

HCID 900320492-((Pyridin-2-ylthio)methyl)-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo-[1,2-a]pyridineYield 74.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

150 mg (0.421 mmol) of 2-(chloromethyl)-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridine were dissolved in 5 ml of acetonitrile followed by the addition of 96 mg (0.842 mmol) of pyridine-2-thiol and 274 mg (0.842 mmol) of cesium carbonate. The solvent was stirred at r.t. for 2 h 30 min. The mixture was then poured into 40 ml of water, and then extracted 3 times with 15 ml of ethyl acetate. The collected organic phases were washed with 30 ml of a saturated sodium hydrogencarbonate solution, with 30 ml of brine and then were dried on Na2SO4 which was then removed by filtration and the obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate gradient, 80% to 70% of heptane, v/v). 129 mg (yield=74%) of 2-((pyridin-2-ylthio)methyl)-3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo-[1,2-a]pyridine were obtained as a beige solid. LC-MS: m/z=410 (MH+) UV purity at 254 nm=99%. 1H NMR (300 MHz, DMSO) δ 8.70 (d, J=6.7 Hz, 1H), 8.52-8.37 (m, 1H), 8.02 (s, 1H), 7.91 (d, J=7.6 Hz, 1H), 7.71 (dd, J=41.7, 4.5 Hz, 4H), 7.43 (s, 2H), 7.13 (d, J=1.1 Hz, 2H), 4.73 (s, 2H).

Workup

  1. extractionextracted 3 times with 15 ml of ethyl acetate
  2. washThe collected organic phases were washed with 30 ml of a saturated sodium hydrogencarbonate solution, with 30 ml of brine
  3. customwere dried on Na2SO4 which
  4. customwas then removed by filtration
  5. concentrationthe obtained filtrate was concentrated in vacuo
  6. customThe crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate gradient, 80% to 70% of heptane, v/v)

Sources & evidence

ORD record
ord-329d0b4582f44aeea26e203f302013df
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

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