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

HRID 1400621ノート

反応式

HRID 1400621 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.C(=O)([O-])[O-].[K+].[K+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.Br[C:37]#[C:38][C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=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:37]#[C:38][C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=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 11430Potassium CarbonateHCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 111483184-Fluorophenylethynyl bromide

生成物 1

HCID 594551558-chloro-5-((4-fluorophenyl)ethynyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole収率 16.4%

試薬・触媒・溶媒 2

HCID 24462Copper Sulfate触媒HCID 1140Toluene溶媒2 回

実験手順

To a stirred solution of 8-chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.2 g, 0.00090 mol) and copper sulfate (0.026 g, 0.00009 mol) in toluene (5 mL) was added potassium carbonate (0.25 g, 0.0018 mol) and 1,10 phenanthroline (0.032 g, 0.000018 mol). The reaction mixture was stirred for 5 min at RT. A solution of 1-bromoethynyl-4-fluoro-benzene (0.199 g, 0.00099 mol) in toluene (2 mL) was added to the reaction mixture. After addition, the reaction mixture was stirred for 2 h at 80° C. After completion of reaction (monitored by TLC), solvent was removed under reduced pressure, and the product obtained was purified by column chromatography (2% MeOH:DCM as eluent on silica (100-200 mesh), diameter of column—5.0 cm, height of silica—approx. 5 inch) to provide the desired compound as a yellow colored oil (0.05 g, 16% yield). The free base was converted to its oxalate salt by treatment with oxalic acid (1 equiv) in THF. 1H NMR (DMSO, oxalate salt) δ (ppm): 7.65 (m, 4H), 7.30 (m, 3H), 4.20 (m, 2H), 3.40 (m, 2H), 3.10 (m, 2H), 2.80 (s, 3H).

後処理

  1. additionAfter addition
  2. stirringthe reaction mixture was stirred for 2 h at 80° C
  3. customAfter completion of reaction (monitored by TLC), solvent
  4. customwas removed under reduced pressure
  5. customthe product obtained
  6. customwas purified by column chromatography (2% MeOH:DCM as eluent on silica (100-200 mesh), diameter of column—5.0 cm, height of silica—approx. 5 inch)

出典と根拠

ORDレコード
ord-bd61edbbd5fe451da8a48a6df17dec56
出典データセット
uspto-grants-2014_12
特許番号
US08906925B2

反応ノート

読み込み中…