Potassium Iodide → Avitriptan

HRID 1647808

反応式

HRID 1647808 の反応式
CS(O[CH2:6][CH2:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH2:18][S:19]([NH:22][CH3:23])(=[O:21])=[O:20])[CH:16]=2)[NH:11][CH:10]=1)(=O)=O.[I-].[K+].C(N(CC)C(C)C)(C)C.[CH3:35][O:36][C:37]1[C:38]([N:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)=[N:39][CH:40]=[N:41][CH:42]=1>C(#N)C>[CH3:35][O:36][C:37]1[C:38]([N:43]2[CH2:48][CH2:47][N:46]([CH2:6][CH2:7][CH2:8][C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[C:15]([CH2:18][S:19]([NH:22][CH3:23])(=[O:21])=[O:20])[CH:16]=4)[NH:11][CH:10]=3)[CH2:45][CH2:44]2)=[N:39][CH:40]=[N:41][CH:42]=1

参加物

6

反応物 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 104201525-Methoxy-4-(piperazin-1-yl)pyrimidineHCID 10713556HCID 10713556、化合物

生成物 1

HCID 133081Avitriptan収率 58%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of crude 3-[5-[[(methylamino)sulfonyl]methyl]-1H-indol-3-yl]propyl methanesulfonate (18.3 mmol, 1.0 equiv.) in 225 mL of anhydrous acetonitrile was added 3.03 g (18.3 mmol, 1.0 equiv.) of potassium iodide, 3.81 mL (21.9 mmol, 1.2 equiv.) of N,N-diisopropylethylamine and 3.89 g (20.1 mmol, 1.1 equiv.) of 1-(5-methoxy-4-pyrimidinyl)piperazine. The mixture was heated to reflux for sixteen hours. The reaction mixture was concentrated in vacuo and the residue was taken up in 500 mL of chloroform. The organic layer was washed with 100 mL portions of 10% potassium carbonate and saturated aqueous sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield an oil. The oil was purified by chromatography on silica gel using 5% methanol in methylene chloride containing 0.5% concentrated aqueous ammonium hydroxide followed by chromatography on silica gel using 20% methanol in ethyl acetate to obtain 4.83 g (58%) of 4-(5-methoxy-4-pyrimidinyl)-1-[3-[5-[[(methylamino)sulfonyl]methyl]-1H-indol-3-yl]propyl]piperazine. The hydrochloride salt was prepared by addition of 3N ethanolic HCl. Two recrystallizations from hot methanol gave 4.05 g (68%) of 4-(5-methoxy-4-pyrimidinyl)-1-[3-[5-[[(methylamino)sulfonyl]methyl]-1H-indol-3-yl]propyl]piperazine hydrochloride, m.p. 170° C. (d). Elemental analysis calculated for C22H30N6O3S/3 HCl: C, 46.52; H, 5.86; N, 14.80; found: C, 46.14; H, 6.22; N, 14.51.

後処理

  1. temperatureThe mixture was heated
  2. temperatureto reflux for sixteen hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. washThe organic layer was washed with 100 mL portions of 10% potassium carbonate and saturated aqueous sodium chloride
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto yield an oil
  9. customThe oil was purified by chromatography on silica gel using 5% methanol in methylene chloride containing 0.5% concentrated aqueous ammonium hydroxide

出典と根拠

ORDレコード
ord-07e147f6222948f9a966671d541e9c3f
出典データセット
uspto-grants-1995_07
特許番号
US05434154

関連ノート

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