Sodium Iodide → 3-[4-[1-(1-Phenyl-1H-indol-3-yl)-4-piperazinyl]butyl]2-methyl-1-thia-3-azaspiro[4.4]nonan-4-one dihydrochloride

HRID 1594798Notes

Reaction equation

HRID 1594798 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[C:9]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[S:8][CH:7]1[CH3:16].[ClH:17].Cl.[C:19]1([N:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([N:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)=[CH:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(C(C)C)CC)(C)C.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CC#N>[ClH:17].[ClH:17].[C:19]1([N:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([N:34]3[CH2:39][CH2:38][N:37]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]4[C:10](=[O:11])[C:9]5([CH2:15][CH2:14][CH2:13][CH2:12]5)[S:8][CH:7]4[CH3:16])[CH2:36][CH2:35]3)=[CH:26]2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 107809503-(4-Bromobutyl)-2-methyl-1-thia-3-azaspiro[4.4]nonan-4-oneHCID 217066021-(1-phenyl-1H-indol-3-yl)piperazine dihydrochloride

Product 1

HCID 148561803-[4-[1-(1-Phenyl-1H-indol-3-yl)-4-piperazinyl]butyl]2-methyl-1-thia-3-azaspiro[4.4]nonan-4-one dihydrochlorideYield 122.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(4-bromobutyl)-2-methyl-1-thia-3-azaspiro[4.4]nonan-4-one (6.80 g), 1-(1-phenyl-1H-indol-3-yl) piperazine dihydrochloride (4.80 g), diisopropylethyl amine (8.16 g), K2CO3 (9.50 g), NaI (400 mg) and CH3CN (200 ml) was heated to 80° C. under nitrogen for 24 hours. The mixture was cooled and filtered, the inorganics were washed with dichlormethane, and the filtrate was concentrated under reduced pressure to a residue. The residue was diluted with 0.5 N NaOH (150 ml) and the aqueous mixture extracted with ether (3×100 ml). The combined ether extracts were washed successively with H2O (150 ml) and brine (150 ml), dried (Na2SO4), and concentrated in vacuo. The crude product was chromatographed on silica gel, eluting with a gradient of 5-10% methanol in dichlormethane. The fractions containing the desired product (Rf=0.42, 10% methanol in dichloromethane) were concentrated to afford 4.84 g of a viscous liquid. The salt of this amine was precipitated from ether by the addition of ethereal HCl. A 4.74 g portion of the salt was recrystallized from ethanol yielding 2.15 g of solid, m.p. 214-217° C.

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washthe inorganics were washed with dichlormethane
  4. concentrationthe filtrate was concentrated under reduced pressure to a residue
  5. additionThe residue was diluted with 0.5 N NaOH (150 ml)
  6. extractionthe aqueous mixture extracted with ether (3×100 ml)
  7. washThe combined ether extracts were washed successively with H2O (150 ml) and brine (150 ml)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude product was chromatographed on silica gel
  11. washeluting with a gradient of 5-10% methanol in dichlormethane
  12. additionThe fractions containing the desired product (Rf=0.42, 10% methanol in dichloromethane)
  13. concentrationwere concentrated

Sources & evidence

ORD record
ord-2159e2c600bf4dcdb68df48cc867364c
Source dataset
uspto-grants-2001_09
Patent number
US06284775B1

Reaction notes

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