Acetic Acid → 1-{4-[4-(4-Chloro-benzyl)-piperazin-1-ylmethyl]-benzyl}-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

HRID 410349노트

반응식

HRID 410349 반응식
[Cl:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.Br.[F:16][C:17]1[CH:45]=[CH:44][C:20]([O:21][CH2:22][CH2:23][CH2:24][N:25]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[N:27]([CH2:34][C:35]3[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=3)[C:26]2=[NH:43])=[CH:19][CH:18]=1.C([BH3-])#N.[Na+].C(O)(=O)C>C1COCC1.O>[Cl:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([CH2:39][C:38]3[CH:37]=[CH:36][C:35]([CH2:34][N:27]4[C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[N:25]([CH2:24][CH2:23][CH2:22][O:21][C:20]5[CH:19]=[CH:18][C:17]([F:16])=[CH:45][CH:44]=5)[C:26]4=[NH:43])=[CH:42][CH:41]=3)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 1348264-ChlorobenzylpiperazineHCID 5003444Sodium cyanoborohydrideHCID 867624844-{3-[3-(4-Fluoro-phenoxy)-propyl]-2-imino-2,3-dihydro-benzoimidazol-1-ylmethyl}-benzaldehyde hydrobromide salt

생성물 1

HCID 585649581-{4-[4-(4-Chloro-benzyl)-piperazin-1-ylmethyl]-benzyl}-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine수율 11.7%

시약·촉매·용매 2

HCID 962Water촉매HCID 8028Tetrahydrofuran용매

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온도
55 °C

실험 절차

To a solution of 1-(4-chloro-benzyl)-piperazine (70 mg, 0.33 mmol) in THF (10 ml) was added 4-{3-[3-(4-fluoro-phenoxy)-propyl]-2-imino-2,3-dihydro-benzoimidazol-1-ylmethyl}-benzaldehyde, hydrobromide salt (0.20 g, 0.41 mmol), sodium cyanoborohydride (31 mg, 0.49 mmol), H2O (1 drop) and glacial acetic acid (0.068 ml). The reaction was warmed to 55° C. where it was maintained for 6 h. After this time, the mixture was cooled to rt and stirred for 16 h. The mixture was concentrated under reduced pressure and then partitioned between 1N HCl and EtOAc. The organic layer was removed and the aqueous phase was made basic using 10% K2CO3. The basic aqueous phase was extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by chromatography on silica eluting with MeOH/dichloromethane provided 1-{4-[4-(4-chloro-benzyl)-piperazin-1-ylmethyl]-benzyl}-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (23 mg, 11%). HPLC-MS 598 [M+1]+, 300.

후처리

  1. temperaturewas maintained for 6 h
  2. temperatureAfter this time, the mixture was cooled to rt
  3. concentrationThe mixture was concentrated under reduced pressure
  4. custompartitioned between 1N HCl and EtOAc
  5. customThe organic layer was removed
  6. extractionThe basic aqueous phase was extracted with EtOAc
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by chromatography on silica eluting with MeOH/dichloromethane

출처 및 근거

ORD 기록
ord-9d2adc9871bb4de7b303e4a4e5b3bdcf
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759520B2

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