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 2361441ノート

反応式

HRID 2361441 の反応式
[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

参加物

4

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 24193Titanium Tetrachloride触媒HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-92d6fefa0bdb4fba828ae88192d07db0
出典データセット
uspto-grants-2014_04
特許番号
US08685969B2

反応ノート

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