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 1776711노트

반응식

HRID 1776711 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
90 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-6326df4c74e1491e8dbf1a68c9419d8e
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09265770B2

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