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 410338ノート

反応式

HRID 410338 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
105 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-210425b00db84b9caaaf70830f98f88e
出典データセット
uspto-grants-2014_06
特許番号
US08759520B2

反応ノート

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