Water → HCID 178436495, compound

HRID 1874939Notes

Reaction equation

HRID 1874939 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:29])=[C:12]([CH2:17][NH:18][C:19]([C:21]3[NH:25][C:24]([CH2:26][CH3:27])=[N:23][C:22]=3[Cl:28])=[O:20])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH:30]([B-](F)(F)F)=[CH2:31].[K+].C(N(CC)CC)C.O>C(O)CC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:28][C:22]1[N:23]=[C:24]([CH2:26][CH3:27])[NH:25][C:21]=1[C:19]([NH:18][CH2:17][C:12]1[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([O:9][C:4]2[CH:3]=[C:2]([CH:30]=[CH2:31])[CH:7]=[C:6]([Cl:8])[CH:5]=2)[C:11]=1[F:29])=[O:20]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 23679353Potassium vinyltrifluoroborateHCID 178437654HCID 178437654, compound

Product 1

HCID 178436495HCID 178436495, compoundYield 82.1%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-2-ethyl-1H-imidazole-5-carboxamide (240 mg, 0.46 mmol), potassium vinyltrifluoroborate (122 mg, 0.92 mmol), PdCl2(dppf)-DCM (15 mg, 0.0184 mmol) and triethylamine (0.13 mL, 0.92 mmol) in n-PrOH (5 mL). The reaction was heated at 100° C. for 6 h, cooled to rt and water was added (20 mL). The aqueous mixture was extracted with EtOAc (3×20 mL) and the organic extracts were combined, dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography (5% to 100% EtOAc/hexanes gradient) to afford the title compound (177 mg, 82%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 8.14 (br s, 1H), 7.47 (d, 1H), 7.35-7.30 (m, 2H), 7.01 (s, 1H), 6.81 (d, 1H), 6.72-6.64 (m, 2H), 5.92 (d, 1H), 5.35 (d, 1H), 4.51 (d, 2H), 2.58 (q, 2H), 1.16 (t, 3H).

Workup

  1. temperaturecooled to rt
  2. extractionThe aqueous mixture was extracted with EtOAc (3×20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by column chromatography (5% to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-f260163194184aeeb1bb8dcb861ab6f7
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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