Potassium Bromide → 1-(2-Chloro-thiazol-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

HRID 410344Notes

Reaction equation

HRID 410344 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[NH:12][C:11]2=[NH:19])=[CH:4][CH:3]=1.[Cl:22][C:23]1[S:24][CH:25]=[C:26]([CH2:28]Cl)[N:27]=1.[Br-].[K+]>CC(=O)CC>[Cl:22][C:23]1[S:24][CH:25]=[C:26]([CH2:28][N:12]2[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:10]([CH2:9][CH2:8][CH2:7][O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:21][CH:20]=3)[C:11]2=[NH:19])[N:27]=1

Participants

5

Reactant 3

HCID 253877Potassium Bromide2×HCID 109208992-Chloro-4-(chloromethyl)-1,3-thiazoleHCID 178509078HCID 178509078, compound

Product 1

HCID 585649551-(2-Chloro-thiazol-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamineYield 61%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 1-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (2.89 g, 10.1 mmol) in 2-butanone (58 ml) at rt was added 2-chloro-4-chloromethyl-thiazole (2.55 g, 15.2 mmol) followed by potassium bromide (1.20 g, 10.1 mmol). The reaction mixture was heated to 95° C. where it was maintained for 32 h. After this time, the reaction was cooled to rt and additional potassium bromide (0.30 g, 2.52 mmol) was introduced. The reaction was stirred for a further 22 h at 90° C. and then it was cooled to rt and filtered. The collected solid was partitioned between dichloromethane and a saturated solution of NaHCO3 (50 ml) and the organic layer was separated. The aqueous phase was extracted with additional dichloromethane (×1) and the combined organic fractions were washed with H2O, brine, dried (Na2SO4), filtered and concentrated under reduced pressure to give 1-(2-chloro-thiazol-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine as a brown oil (2.57 g, 61%). HPLC-MS 417 [M+1]+.

Workup

  1. temperaturewas maintained for 32 h
  2. temperatureAfter this time, the reaction was cooled to rt
  3. temperatureit was cooled to rt
  4. filtrationfiltered
  5. customThe collected solid was partitioned between dichloromethane
  6. customa saturated solution of NaHCO3 (50 ml) and the organic layer was separated
  7. extractionThe aqueous phase was extracted with additional dichloromethane (×1)
  8. washthe combined organic fractions were washed with H2O, brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7ca7c1f32cc344409ec3a283c5a2e235
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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