Potassium Hydroxide → 8-Isopropyl-2-methyl-5-[2-(5-methyl-pyrazin-2-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 2195948

反応式

HRID 2195948 の反応式
[CH:1]([C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1)([CH3:3])[CH3:2].[OH-].[K+].[CH3:20][C:21]1[CH:26]=[N:25][C:24]([CH:27]=[CH2:28])=[CH:23][N:22]=1>CN1CCCC1=O.O>[CH:1]([C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH2:28][CH2:27][C:24]3[CH:23]=[N:22][C:21]([CH3:20])=[CH:26][N:25]=3)[C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1)([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 14797Potassium HydroxideHCID 263352-Methyl-5-vinylpyrazineHCID 594552192,3,4,5-tetrahydro-8-isopropyl-2-methyl-1H-pyrido[4,3-b]indole

生成物 1

HCID 578762328-Isopropyl-2-methyl-5-[2-(5-methyl-pyrazin-2-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole収率 16.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

To a solution of 8-Isopropyl-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.2 g. 0.87 mmol) in N-methyl 2-pyrolidone (1.0 mL) was added powdered potassium hydroxide (0.5 g, 8.7 mmol) and allowed to stir for 10 min at RT. 2-methyl-5-vinyl pyrazine (0.25 g, 2.1 mmol) was added and stirred for further 5 h. at 60 deg C. After completion (TLC), reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3×100 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure using rotary evaporator. The crude was purified through column chromatography (6% MeOH:DCM in silica 100-200 mesh, Diameter of column 2.5 cm, Height of silica—approx. 5 inch) then further purified through preparative TLC to provide the desired compound as yellow solid (0.05 g, 16% yield). 8-Isopropyl-2-methyl-5-[2-(5-methyl-pyrazin-2-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.05 g, 0.143 mmol) was dissolved in THF (2.0 mL). A solution of oxalic acid dihydrate (0.018 g, 0.143 mmol) in THF (1.0 mL) was added and stirred for 30 min at RT, Precipitate obtained was filtered and dried to give oxalate salt as off white solid (0.02 g, 32% yield).

後処理

  1. stirringstirred for further 5 h. at 60 deg C
  2. customAfter completion (TLC), reaction mixture
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customevaporator
  7. customThe crude was purified through column chromatography (6% MeOH:DCM in silica 100-200 mesh, Diameter of column 2.5 cm, Height of silica—approx. 5 inch)
  8. customthen further purified through preparative TLC

出典と根拠

ORDレコード
ord-3de80732470f47349ec8ea716da9d85f
出典データセット
uspto-grants-2012_12
特許番号
US08338408B2

関連ノート

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