8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → (Z)-8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400546ノート

反応式

HRID 1400546 の反応式
Br[CH:2]=[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[CH3:4].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.[Cl:28][C:29]1[CH:37]=[CH:36][C:35]2[NH:34][C:33]3[CH2:38][CH2:39][N:40]([CH3:42])[CH2:41][C:32]=3[C:31]=2[CH:30]=1>CN(C=O)C.[Cu]I>[Cl:28][C:29]1[CH:37]=[CH:36][C:35]2[N:34](/[CH:2]=[C:3](\[C:5]3[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=3)/[CH3:4])[C:33]3[CH2:38][CH2:39][N:40]([CH3:42])[CH2:41][C:32]=3[C:31]=2[CH:30]=1

参加物

7

反応物 4

HCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

生成物 1

HCID 46199580(Z)-8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

1-(1-Bromoprop-1-en-2-yl)-4-fluorobenzene (511.2 mg, 2.4 mmol) was dissolved in DMF. Potassium phosphate (848 mg, 4 mmol) was added followed by the addition of copper (I)iodide (38 mg, 0.2 mmol) and L-proline (46 mg, 0.4 mmol). 8-chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (440 mg, 2 mmol) was added to the reaction mixture and nitrogen gas purged for 2 min. The reaction mixture was heated at 85° C. overnight. The reaction mixture was cooled to RT and ice water was added. Solid mass was filtered under vacuum and crude purified by silica gel chromatography using 0-3% MeOH:DCM as eluent. Two isomers were further purified through reverse phase HPLC and peak 1 was submitted as the final compound. Yield: 120 mg. 1H NMR (DMSO, HCl salt) δ (ppm): 7.50 (s, 1H), 7.10-6.95 (m, 6H), 6.82 (s, 1H), 4.50 (m, 1H), 4.20 (m, 1H), 3.60 (m, 2H), 2.85 (s, 3H), 2.80 (m, 2H), 2.25 (s, 3H).

後処理

  1. custompurged for 2 min
  2. temperatureThe reaction mixture was cooled to RT
  3. additionice water was added
  4. filtrationSolid mass was filtered under vacuum and crude
  5. custompurified by silica gel chromatography
  6. customTwo isomers were further purified through reverse phase HPLC and peak 1

出典と根拠

ORDレコード
ord-003a3fcf2100469b8f055cff7ab1cb42
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…