Ethyl 2-((4-bromo-7-cyano-1H-indol-3-yl)methylamino)-3,3-diethoxypropanoate → ethyl 9-bromo-6-cyano-5H-pyrido[4,3-b]indole-3-carboxylate

HRID 2361441노트

반응식

HRID 2361441 반응식
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[C:7]2[C:3]=1[C:4]([CH2:13][NH:14][CH:15]([CH:21](OCC)OCC)[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5][NH:6]2>C1(C)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[C:3]2[C:4]3[CH:13]=[N:14][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:21][C:5]=3[NH:6][C:7]=2[C:8]([C:11]#[N:12])=[CH:9][CH:10]=1

참가 물질

4

반응물 1

HCID 67995067Ethyl 2-((4-bromo-7-cyano-1H-indol-3-yl)methylamino)-3,3-diethoxypropanoate

생성물 1

HCID 67995622ethyl 9-bromo-6-cyano-5H-pyrido[4,3-b]indole-3-carboxylate수율 34.1%

시약·촉매·용매 2

HCID 24193Titanium Tetrachloride촉매HCID 1140Toluene용매

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온도
90 °C

실험 절차

To a solution of ethyl 2-(((4-bromo-7-cyano-1H-indol-3-yl)methyl)amino)-3,3-diethoxypropanoate (1.12 g, 2.56 mmol) in toluene (51.1 mL) at 0° C. was added dropwise titanium tetrachloride (1 M in CH2Cl2, 8.94 mL, 8.94 mmol). The mixture was heated at 90° C. for 3 h. The mixture was cooled to room temperature and partitioned between NaHCO3 (aq) and EtOAc. The organic phase was washed with brine, dried and concentrated. The resulting dark yellow solid was suspended in methanol, then collected by filtration and air-dried to afford the desired product as a yellow solid (300 mg, 29% yield), contaminated with partially aromatized material (ethyl 9-bromo-6-cyano-4,5-dihydro-3H-pyrido[4,3-b]indole-3-carboxylate and/or ethyl 9-bromo-6-cyano-2,5-dihydro-1H-pyrido[4,3-b]indole-3-carboxylate) and ethyl 9-bromo-6-cyano-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-3-carboxylate, which was used without further purification. LCMS (M+H)+ m/z 343.9, 345.9.

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between NaHCO3 (aq) and EtOAc
  3. washThe organic phase was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. filtrationcollected by filtration
  7. customair-dried

출처 및 근거

ORD 기록
ord-92d6fefa0bdb4fba828ae88192d07db0
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685969B2

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