Diisopropylethylamine → 1-[3-(5-cyano-1H-indol-3-yl)propyl]-4-(5-methoxy-4-pyrimidinyl)piperazine

HRID 1463355Notes

Reaction equation

HRID 1463355 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]#[N:19])[CH:16]=2)[NH:11][CH:10]=1)(=O)=O.[CH3:20][O:21][C:22]1[C:23]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[N:24][CH:25]=[N:26][CH:27]=1.C(N(CC)C(C)C)(C)C>C(#N)C.C(Cl)(Cl)Cl>[C:18]([C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[C:9]2[CH2:8][CH2:7][CH2:6][N:31]1[CH2:32][CH2:33][N:28]([C:23]2[C:22]([O:21][CH3:20])=[CH:27][N:26]=[CH:25][N:24]=2)[CH2:29][CH2:30]1)#[N:19]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 104201525-Methoxy-4-(piperazin-1-yl)pyrimidineHCID 19921678HCID 19921678, compound

Product 1

HCID 99515961-[3-(5-cyano-1H-indol-3-yl)propyl]-4-(5-methoxy-4-pyrimidinyl)piperazineYield 42.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-(5-cyano-1H-indol-3-yl)propyl methanesulfonate (2.35 mmol, 1.0 equiv.) in 25 mL of anhydrous acetonitrile was added 0.874 g (4.5 mmol, 1.5 equiv.) of (5-methoxy-4-pyrimidinyl)piperazine and 1.0 mL of N,N-diisopropylethylamine. The mixture was heated to reflux for thirteen hours. The solution was cooled, diluted with 100 mL of chloroform and washed once with 20 mL of 10% aqueous sodium carbonate. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel using 5% methanol in methylene chloride containing 0.5% concentrated aqueous ammonium hydroxide to yield 0.375 g (42%, two steps) of 1-[3-(5-cyano-1H-indol-3-yl) propyl]-4-(5-methoxy-4-pyrimidinyl)piperazine pure by 1H NMR analysis.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for thirteen hours
  3. temperatureThe solution was cooled
  4. washwashed once with 20 mL of 10% aqueous sodium carbonate
  5. customThe organic layer was separated
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed on silica gel using 5% methanol in methylene chloride containing 0.5% concentrated aqueous ammonium hydroxide

Sources & evidence

ORD record
ord-c21808c6ef2348d99c84af8f9e11a288
Source dataset
uspto-grants-1994_04
Patent number
US05300506

Reaction notes

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