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

HRID 410338노트

반응식

HRID 410338 반응식
Br[C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]([CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[C:8]2=[NH:27])=[CH:4][CH:3]=1.[Cl:30][C:31]1[CH:43]=[CH:42][C:34]([CH2:35][N:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)=[CH:33][CH:32]=1.CC(C)([O-])C.[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:30][C:31]1[CH:43]=[CH:42][C:34]([CH2:35][N:36]2[CH2:41][CH2:40][N:39]([C:2]3[CH:29]=[CH:28][C:5]([CH2:6][N:7]4[C:11]5[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=5[N:9]([CH2:16][CH2:17][CH2:18][O:19][C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=5)[C:8]4=[NH:27])=[CH:4][CH:3]=3)[CH2:38][CH2:37]2)=[CH:33][CH:32]=1

참가 물질

7

반응물 4

HCID 1348264-ChlorobenzylpiperazineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 462409921-(4-Bromo-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

생성물 1

HCID 462417081-{4-[4-(4-Chloro-benzyl)-piperazin-1-yl]-benzyl}-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine수율 18%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

반응 조건

온도
105 °C

실험 절차

To a solution 1-(4-bromo-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (0.25 g, 0.55 mmol) in toluene (20 ml) was added 1-(4-chloro-benzyl)-piperazine (0.16 g, 0.55 mmol), potassium t-butoxide (216 mg, 1.93 mmol), Pd2(dba)3 (35 mg, 0.038 mmol) and BINAP (48 mg, 0.077 mmol). Nitrogen was bubbled through the suspension for 5 min and then the reaction was heated to 105° C. for 24 h. After this time, the mixture was cooled to rt and filtered. The collected solids were washed with additional toluene and then the combined filtrate and washings were concentrated under reduced pressure. The crude product was purified by chromatography on silica to provide 1-{4-[4-(4-chloro-benzyl)-piperazin-1-yl]-benzyl}-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (57 mg, 18%). HPLC-MS 584 [M+1]+, 293.

후처리

  1. customNitrogen was bubbled through the suspension for 5 min
  2. temperatureAfter this time, the mixture was cooled to rt
  3. filtrationfiltered
  4. washThe collected solids were washed with additional toluene
  5. concentrationthe combined filtrate and washings were concentrated under reduced pressure
  6. customThe crude product was purified by chromatography on silica

출처 및 근거

ORD 기록
ord-210425b00db84b9caaaf70830f98f88e
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759520B2

반응 노트

불러오는 중…