Potassium Iodide → Avitriptan

HRID 1647808

Reaction equation

HRID 1647808 reaction equation
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

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 104201525-Methoxy-4-(piperazin-1-yl)pyrimidineHCID 10713556HCID 10713556, compound

Product 1

HCID 133081AvitriptanYield 58%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-07e147f6222948f9a966671d541e9c3f
Source dataset
uspto-grants-1995_07
Patent number
US05434154

Linked notes

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