Triethylamine → HCID 178436400, compound

HRID 1875124Notes

Reaction equation

HRID 1875124 reaction equation
[CH3:1][CH2:2]N(CC)CC.Br[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]([C:19]2[NH:23][C:22]([CH3:24])=[N:21][C:20]=2[Cl:25])=[O:18])=[C:11]([F:26])[C:10]=1[O:27][C:28]1[CH:33]=[C:32]([C:34]#[N:35])[CH:31]=[C:30]([Cl:36])[CH:29]=1.C([B-](F)(F)F)=C.[K+]>C(O)CC>[Cl:25][C:20]1[N:21]=[C:22]([CH3:24])[NH:23][C:19]=1[C:17]([NH:16][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([CH:1]=[CH2:2])=[C:10]([O:27][C:28]2[CH:33]=[C:32]([C:34]#[N:35])[CH:31]=[C:30]([Cl:36])[CH:29]=2)[C:11]=1[F:26])=[O:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 23679353Potassium vinyltrifluoroborateHCID 178432867HCID 178432867, compound

Product 1

HCID 178436400HCID 178436400, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

Et3N (0.351 ml, 2.52 mmol) was added to a mixture of N-({4-bromo-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-4-chloro-2-methyl-1H-imidazole-5-carboxamide (251 mg, 0.504 mmol), potassium vinyltrifluoroborate (101 mg, 0.756 mmol) and 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloride dichloromethane complex (41.1 mg, 0.050 mmol) in n-propanol (5 ml) under N2. The mixture was heated to 100° C. and stirred for 4 h. Cooled down to RT and the reaction mixture was filtered through a pad of celite and concentrated to dryness. The residue was dissolved in EtOAC, washed with Sat. NaHCO3, dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on silica gel eluted with 0-5% 2M NH3 solution of MeOH in CH2Cl2 to give the title compound as a light-yellow solid (154 mg, 69%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.33 (1H, br. s.) 7.40 (1H, d, J=8.2 Hz) 7.31 (1H, s) 7.26-7.29 (1H, m) 7.12 (2H, br. s.) 6.98 (1H, s) 6.69 (1H, dd, J=17.6, 11.2 Hz) 5.81 (1H, d, J=17.6 Hz) 5.37 (1H, d, J=11.1 Hz) 4.70 (2H, d, J=5.9 Hz) 2.39 (3H, s). LCMS: m/z 445 (M+1).

Workup

  1. temperatureCooled down to RT
  2. filtrationthe reaction mixture was filtered through a pad of celite
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in EtOAC
  5. washwashed with Sat. NaHCO3
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by chromatography on silica gel
  9. washeluted with 0-5% 2M NH3 solution of MeOH in CH2Cl2

Sources & evidence

ORD record
ord-5a810d38ad024b99a0e1a13ca72bf7df
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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