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

HRID 1400623ノート

反応式

HRID 1400623 の反応式
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH: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]>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([C:39]#[C:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[C:43]([F:49])[CH:42]=3)[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

参加物

7

反応物 4

HCID 13181,10-PhenanthrolineHCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 62657Potassium Phosphate, TribasicHCID 59455074HCID 59455074、化合物

生成物 1

HCID 594551878-chloro-5-((3-fluoro-4-methoxyphenyl)ethynyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole収率 12.1%

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

8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (100 mg, 0.45 mmol) was dissolved in toluene (5 mL). Copper sulfate (23 mg, 0.090 mmol), 1,10-phenanthroline (33 mg, 0.18 mmol), potassium phosphate (192 mg, 0.90 mmol), and 4-(bromoethynyl)-2-fluoro-1-methoxybenzene (113 mg, 0.49 mmol) were added, and the mixture was 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 reduced pressure to obtain product, which was purified by column chromatography using silica gel and 60-80% EtOAc in hexane as eluent, and repurified by preparative TLC to obtain product as a brown solid (20 mg). 1H NMR (DMSO, oxalate salt) δ (ppm): 7.70 (d, 2H), 7.58 (d, 1H), 7.42 (d, 1H), 7.38 (d, 1H), 7.25 (m, 1H), 4.20 (m, 2H), 3.85 (s, 3H), 3.40 (m, 2H), 3.10 (m, 2H), 2.80 (s, 3H).

後処理

  1. customthe mixture was flushed with nitrogen
  2. filtrationThe reaction mixture was filtered through Celite
  3. washwashed with DCM
  4. concentrationThe combined organic layer was concentrated under reduced pressure
  5. customto obtain product, which
  6. customwas purified by column chromatography
  7. customrepurified by preparative TLC

出典と根拠

ORDレコード
ord-c551441288aa47638630b0a4dceff098
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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