Sodium Iodide → 6-Butyl-8-[(1-{2-[(1,1-di methylethyl)sulfonyl]ethyl}-4-piperidinyl)oxy]quinoline, dihydrochloride salt

HRID 1363019Notes

Reaction equation

HRID 1363019 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4].[I-].[Na+].C(=O)(O)[O-].[Na+].[CH3:29][C:30]([S:33]([CH2:36][CH2:37][Cl:38])(=[O:35])=[O:34])([CH3:32])[CH3:31]>CN(C=O)C.CO>[ClH:38].[ClH:38].[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:17][CH2:18][N:19]([CH2:37][CH2:36][S:33]([C:30]([CH3:32])([CH3:31])[CH3:29])(=[O:35])=[O:34])[CH2:20][CH2:21]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 301277Propane, 2-[(2-chloroethyl)sulfonyl]-2-methyl-2×HCID 516892Sodium BicarbonateHCID 579260486-Butyl-8-(4-piperidinyloxy)quinoline2×

Product 1

HCID 1317286506-Butyl-8-[(1-{2-[(1,1-di methylethyl)sulfonyl]ethyl}-4-piperidinyl)oxy]quinoline, dihydrochloride saltYield 8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 6-butyl-8-(4-piperidinyloxy)quinoline (for example, as prepared for Intermediate 4) (80 mg, 0.28 mmol), sodium iodide (37 mg, 0.25 mmol), sodium bicarbonate (168 mg, 2.0 mmol) and 2-chloroethyl 1,1-dimethylethyl sulfone (for example, as prepared for Intermediate 12) (208 mg, 1.1 mmol) in DMF (2 ml) was heated at 150° C. for 15 min in a Smith Creator™ microwave oven. The reaction mixture was applied to an SCX-2 cartridge (20 g) preconditioned with methanol and was eluted with methanol, followed by 10% aqueous 0.88 s.g. ammonia in methanol. The ammoniacal fractions were combined and concentrated in vacuo and the residue (118 mg) was purified by MDAP (×2). Appropriate fractions were combined and concentrated in vacuo to give the free base of the title compound (10 mg, 8%): This was diluted with methanol and treated with 1.25 M hydrogen chloride solution in methanol (0.05 ml) and the solution was evaporated in vacuo to give the title compound (12 mg): LCMS RT=2.73 min, ES+ve m/z 433 (M+H)+.

Workup

  1. washwas eluted with methanol
  2. customfollowed by 10% aqueous 0.88 s
  3. concentrationconcentrated in vacuo
  4. customthe residue (118 mg) was purified by MDAP (×2)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f29db25e001a40149069f99e6153b92c
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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