Sodium Iodide → 6-Butyl-8-({1-[3-(methylsulfonyl)propyl]-4-piperidinyl}oxy)quinoline, dihydrochloride salt

HRID 1363020Notes

Reaction equation

HRID 1363020 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][S:30]([CH2:33][CH2:34][CH2:35]Br)(=[O:32])=[O:31].CS(CCC[Cl:44])(=O)=O>CN(C=O)C.CO>[ClH:44].[ClH:44].[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]([CH2:35][CH2:34][CH2:33][S:30]([CH3:29])(=[O:32])=[O:31])[CH2:20][CH2:21]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 138750421-Chloro-3-methanesulfonylpropane2×HCID 518920821-Bromo-3-methanesulfonylpropaneHCID 579260486-Butyl-8-(4-piperidinyloxy)quinoline2×

Product 1

HCID 1317286516-Butyl-8-({1-[3-(methylsulfonyl)propyl]-4-piperidinyl}oxy)quinoline, dihydrochloride saltYield 18%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

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 (30 mg, 0.2 mmol) and sodium bicarbonate (110 mg, 1.3 mmol) in DMF (2 ml) was treated with a solution of mixture of 3-bromopropyl methyl sulfone and 3-chloropropyl methyl sulfone (for example, as prepared for Intermediate 19) (124 mg) in DMF (0.5 ml) and the mixture was heated at 150° C. for 15 min in a Smith Creator™ microwave oven. The reaction mixture was applied to an SCX-2 cartridge (10 g), preconditioned with methanol, and 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 (126 mg) was purified by MDAP. Appropriate fractions were combined and concentrated in vacuo and the residue (30 mg) was applied to an SCX-2 cartridge (5 g), pre-conditioned with methanol and eluted with methanol, followed by 10% aqueous 0.88 s.g. ammonia in methanol. The ammoniacal fractions were combined and concentrated in vacuo to give the free base of the title compound (21 mg, 18%): This was treated with 1.25 M hydrogen chloride solution in methanol (0.15 ml) and the solution was evaporated in vacuo to give the title compound (22 mg, 89%): LCMS RT=2.49 min, ES+ve m/z 405 (M+H)+.

Workup

  1. washeluted with methanol
  2. customfollowed by 10% aqueous 0.88 s
  3. concentrationconcentrated in vacuo
  4. customthe residue (126 mg) was purified by MDAP
  5. concentrationconcentrated in vacuo
  6. washeluted with methanol
  7. customfollowed by 10% aqueous 0.88 s
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-60a9677521dc4467879e6d15d97e4813
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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