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

HRID 410344노트

반응식

HRID 410344 반응식
[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

참가 물질

5

반응물 3

HCID 253877Potassium Bromide2회HCID 109208992-Chloro-4-(chloromethyl)-1,3-thiazoleHCID 178509078HCID 178509078, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6569Methyl Ethyl Ketone용매

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온도
95 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-7ca7c1f32cc344409ec3a283c5a2e235
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759520B2

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