N-[2-(5-bromo-1-indolinyl)-5-methylphenyl]-4-methyl-1-piperazinecarboxamide → 4-Bromo-6-(4-methyl-1-piperazinyl)-9-methyl-1,2-dihydrobenzo[b]-pyrrolo [3,2,1-jk][1,4]benzodiazepine

HRID 4031

반응식

HRID 4031 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][C:12]=1[NH:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1)=O)[CH2:6][CH2:5]2>P(Cl)(Cl)(Cl)=O>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:5][CH2:6][N:7]3[C:8]2=[C:9]([CH:10]=1)[C:19]([N:21]1[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1)=[N:18][C:12]1[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:11]=13

참가 물질

3

반응물 1

HCID 13823367N-[2-(5-bromo-1-indolinyl)-5-methylphenyl]-4-methyl-1-piperazinecarboxamide

생성물 1

HCID 138233144-Bromo-6-(4-methyl-1-piperazinyl)-9-methyl-1,2-dihydrobenzo[b]-pyrrolo [3,2,1-jk][1,4]benzodiazepine수율 53.9%

시약·촉매·용매 1

HCID 24813Phosphorus oxychloride용매

실험 절차

A solution of N-[2-(5-bromo-1-indolinyl)-5-methylphenyl]-4-methyl-1-piperazinecarboxamide (3.3 g, 7.68 mmoles) and phosphorus oxychloride (30 ml) was heated at reflux for 25 minutes under nitrogen. The solution was cooled and excess phosphorus oxychloride was removed at 55°-60° C. under vacuum. Ice-chilled 2N-sodium hydroxide solution (100 ml) and dichloromethane (250 ml) were added to the residue. The organic phase was separated and washed with brine (2 times, 100 ml), dried over anhydrous magnesium sulfate, and concentrated. Purification was accomplished by flash chromatography over aluminum oxide (Grade III, 100 g), eluted with dichloromethane (2 l). The fractions containing pure material were pooled and concentrated. Recrystallization from isopropanol (30 ml) yielded 1.7 g (53.9%) of product, mp 187°-189° C.

후처리

  1. temperatureat reflux for 25 minutes under nitrogen
  2. temperatureThe solution was cooled
  3. customexcess phosphorus oxychloride was removed at 55°-60° C. under vacuum
  4. temperatureIce-chilled 2N-sodium hydroxide solution (100 ml) and dichloromethane (250 ml)
  5. additionwere added to the residue
  6. customThe organic phase was separated
  7. washwashed with brine (2 times, 100 ml)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customPurification
  11. washeluted with dichloromethane (2 l)
  12. additionThe fractions containing pure material
  13. concentrationconcentrated
  14. customRecrystallization from isopropanol (30 ml)

출처 및 근거

ORD 기록
ord-cbb4808b692a4f609145ab6de26bd51d
출처 데이터셋
uspto-grants-1988_02
특허 번호
US04723007

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