Sodium Chloride → HCID 73051807, compound

HRID 1048710Notes

Reaction equation

HRID 1048710 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][O:12][C:13]1[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16].[C:23]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)#[CH:24].C(N(CC)CC)C.[Na+].[Cl-]>CN(C)C=O.[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]>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:23]#[C:24][C:2]2[N:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]3=[N:4][C:3]=2[CH2:11][O:12][C:13]2[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=2[C:15]([O:17][CH3:18])=[O:16])=[CH:26][CH:27]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 8471TriethylamineHCID 5226271-Ethynyl-4-fluorobenzeneHCID 118195059HCID 118195059, compound

Product 1

HCID 73051807HCID 73051807, compoundYield 88.9%

Reagents, catalysts & solvents 3

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

Procedure

In a flask placed under an argon flow, 2 g (3.82 mmol) of methyl 2-((3-iodoimidazo[1,2-a]pyridin-2-yl)methoxy)benzoate were dissolved in 8 ml of dimethylformamide with magnetic stirring. To this solution were added: 0.074 g (0.382 mmol) of copper iodide, 0.551 g (4.59 mmol) of 1-ethynyl-4-fluorobenzene and 8 ml (57.3 mmol) of triethylamine. The reaction medium was degassed with argon for 10 min before adding 0.35 g (0.382 mmol) of Pd2(dba)3. The mixture was stirred at r.t. for 16 h before being treated with 100 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 2×100 ml of ethyl acetate. The combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution, 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: heptane/ethyl acetate, 1/1, v/v). 1.36 g (yield=84%) of methyl 2-((3-((4-fluorophenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl)methoxy)benzoate were obtained as a pale brown solid. LC-MS: m/z=401 (MH+); UV purity at 254 nm=98%. 1H NMR (300 MHz, DMSO) δ 8.63 (d, J=6.7 Hz, 1H), 7.75-7.59 (m, 4H), 7.48 (ddd, J=15.9, 11.5, 4.8 Hz, 2H), 7.40-7.26 (m, 3H), 7.13 (t, J=6.8 Hz, 1H), 7.01 (t, J=7.4 Hz, 1H), 5.40 (s, 2H), 3.68 (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. extractionThe aqueous phase was extracted with 2×100 ml of ethyl acetate
  5. washThe combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution
  6. customdried on Na2SO4 which
  7. customwas then removed by filtration
  8. concentrationThe obtained filtrate was concentrated in vacuo
  9. customThe crude residue was purified by flash chromatography on a silica gel cartridge (eluent

Sources & evidence

ORD record
ord-d734f3e4c1b74ae893a151712cc8642d
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

Loading…