diethyl (1S,2S)-3,3-dimethylcyclopropane-1,2-dicarboxylate → racemic trans-Ethyl 3-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylcyclopropanecarboxylate

HRID 1776711ノート

反応式

HRID 1776711 の反応式
C[Al](C)C.[Br:5][C:6]1[CH:32]=[CH:31][C:9]([CH2:10][NH:11][C:12]2[C:13]([NH2:30])=[CH:14][C:15]([O:18][CH2:19][C:20]3[CH:29]=[CH:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)=[CH:16][CH:17]=2)=[CH:8][CH:7]=1.[CH3:33][C:34]1([CH3:47])[C@@H:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[C@@H:35]1[C:42](OCC)=O>C(Cl)Cl>[Br:5][C:6]1[CH:32]=[CH:31][C:9]([CH2:10][N:11]2[C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]4[CH:29]=[CH:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[N:21]=4)=[CH:14][C:13]=3[N:30]=[C:42]2[C@H:35]2[C@H:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[C:34]2([CH3:33])[CH3:47])=[CH:8][CH:7]=1

参加物

5

反応物 3

HCID 2724581diethyl (1S,2S)-3,3-dimethylcyclopropane-1,2-dicarboxylateHCID 16682925TrimethylaluminumHCID 90414798N1-(4-bromobenzyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine

生成物 1

HCID 117606232racemic trans-Ethyl 3-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylcyclopropanecarboxylate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

A solution of trimethyl aluminum (0.2 mL, 2 M in toluene) was added to 25 mL round-bottomed flask containing N1-(4-bromobenzyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine (100 mg, 0.23 mmol), trans-diethyl 3,3-dimethylcyclopropane-1,2-dicarboxylate (49 mg, 0.23 mmol), and DCM (4 mL). After 12 h, the solution was partitioned between sat. NaHCO3 (30 mL) and EtOAc (30 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combine organic layers were dried with sodium sulfate, filtered, and concentrated to dryness. To the residue was added ethanol (2 mL) and concentrated HCl (0.1 mL, 12 N). The solution heated to 90° C. After 5 h, the mixture was cooled, concentrated to dryness, and purified by reverse phase HPLC to afford the title compound. MS (ESI): mass calcd. for C32H30BrN3O3, 583.15; m/z found, 584.1 [M+H]+.

後処理

  1. customthe solution was partitioned between sat. NaHCO3 (30 mL) and EtOAc (30 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  4. dry with materialThe combine organic layers were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. additionTo the residue was added ethanol (2 mL) and concentrated HCl (0.1 mL, 12 N)
  8. waitAfter 5 h
  9. temperaturethe mixture was cooled
  10. concentrationconcentrated to dryness
  11. custompurified by reverse phase HPLC

出典と根拠

ORDレコード
ord-6326df4c74e1491e8dbf1a68c9419d8e
出典データセット
uspto-grants-2016_02
特許番号
US09265770B2

反応ノート

読み込み中…