1,10-Phenanthroline → 5-((3-fluoro-4-methoxyphenyl)ethynyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400631ノート

反応式

HRID 1400631 の反応式
[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:39]#[C:40][C:41]1[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[C:43]([F:49])[CH:42]=1>C1(C)C=CC=CC=1.S([O-])([O-])(=O)=O.[Cu+2]>[F:49][C:43]1[CH:42]=[C:41]([C:40]#[C:39][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]2=3)[CH:46]=[CH:45][C:44]=1[O:47][CH3:48]

参加物

7

反応物 4

HCID 13181,10-PhenanthrolineHCID 62657Potassium Phosphate, TribasicHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 59455074HCID 59455074、化合物

生成物 1

HCID 594548915-((3-fluoro-4-methoxyphenyl)ethynyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole収率 7.6%

試薬・触媒・溶媒 2

HCID 24462Copper Sulfate触媒HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

2,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (100 mg, 0.49 mmol) was dissolved in toluene (5 mL), and copper sulfate (24 mg, 0.099 mmol) was added, followed by 1,10-phenanthroline (35 mg, 0.19 mmol), potassium phosphate (0.211 mg, 0.99 mmol) and 4-(bromoethynyl)-2-fluoro-1-methoxybenzene (125 mg, 0.54 mmol), and the mixture flushed with nitrogen. The reaction mixture was heated at 80° C. overnight (16 h). Product was detected by LCMS. The reaction mixture was filtered through Celite, and washed with DCM. The combined organic layer was concentrated under vacuum to obtain product which was purified by column chromatography (60-80% EtOAc in hexane as eluent), and repurified by preparative TLC to obtain product as a brown solid (13 mg). 1H NMR (CDCl3, freebase) δ (ppm): 7.42 (d, 1H), 7.25 (m, 2H), 7.18 (s, 1H), 7.10 (d, 1H), 6.92 (t, 1H), 3.95 (s, 3H), 3.62 (s, 2H), 2.95 (m, 2H), 2.85 (m, 2H), 2.60 (s, 3H), 2.40 (s, 3H).

後処理

  1. customthe mixture flushed with nitrogen
  2. filtrationThe reaction mixture was filtered through Celite
  3. washwashed with DCM
  4. concentrationThe combined organic layer was concentrated under vacuum
  5. customto obtain product which
  6. customwas purified by column chromatography (60-80% EtOAc in hexane as eluent)
  7. customrepurified by preparative TLC

出典と根拠

ORDレコード
ord-d947d9df4fad418f9d61aa5e3dd82920
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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