4-Bromopyrimidine → 2,8-dimethyl-5-(pyrimidin-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400644ノート

反応式

HRID 1400644 の反応式
[C:1]([N:3]1[C:11]2[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=2[C:5]2[CH2:13][N:14]([CH3:17])[CH2:15][CH2:16][C:4]1=2)#[CH:2].Br[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][N:20]=1>C(N(CC)CC)C.[Cu](I)I>[CH3:17][N:14]1[CH2:15][CH2:16][C:4]2[N:3]([C:1]#[C:2][C:19]3[CH:24]=[CH:23][N:22]=[CH:21][N:20]=3)[C:11]3[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=3[C:5]=2[CH2:13]1

参加物

5

反応物 2

HCID 127522204-BromopyrimidineHCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

生成物 1

HCID 594550372,8-dimethyl-5-(pyrimidin-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole収率 17.7%

試薬・触媒・溶媒 2

HCID 83717Copper iodide触媒HCID 8471Triethylamine溶媒

反応条件

温度
40 °C

実験手順

5-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (100 mg, 0.466 mmol) and 4-bromopyrimidine (126 mg, 0.797 mmol) were dissolved in triethylamine (1.5 mL), and the solution was purged with nitrogen. Dichlorobis (triphenylphosphine) palladium (12.5 mg, 0.017 mmol) and copper iodide (6.7 mg, 0.035 mmol) were added and the reaction mixture was purged again with nitrogen. The reaction mixture was heated by microwave at 40° C. for 90 min. The reaction mixture was quenched with 30 mL water and extracted with EtOAc (3×15 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to obtain crude product. The crude product was purified with column chromatography (silica gel: 100-200 mesh, eluent 0-10% MeOH in DCM) to obtain 25 mg product. 1H NMR (CDCl3, freebase) δ (ppm): 9.17 (s, 1H), 8.76 (d, 1H), 7.57 (d, 1H), 7.40 (d, 1H), 7.18 (m, 2H), 3.64 (s, 2H), 3.06 (d, 2H), 2.98 (d, 2H), 2.61 (s, 3H), 2.43 (s, 3H).

後処理

  1. customthe solution was purged with nitrogen
  2. customthe reaction mixture was purged again with nitrogen
  3. customThe reaction mixture was quenched with 30 mL water
  4. extractionextracted with EtOAc (3×15 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto obtain crude product
  8. customThe crude product was purified with column chromatography (silica gel: 100-200 mesh, eluent 0-10% MeOH in DCM)

出典と根拠

ORDレコード
ord-d7a6c9e5539e448097fef8aef7cdf3eb
出典データセット
uspto-grants-2014_12
特許番号
US08906925B2

反応ノート

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