Sodium Iodide → 6-Butyl-8-[(1-{3-[(1,1-di methylethyl)sulfonyl]propyl}-4-piperidinyl)oxy]quinoline, formate salt

HRID 1363021Notes

Reaction equation

HRID 1363021 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:24](=O)([OH:26])[O-:25].[Na+].[CH3:29][C:30]([S:33]([CH2:36][CH2:37][CH2:38]Br)(=[O:35])=[O:34])([CH3:32])[CH3:31].CC(S(CCCCl)(=O)=O)(C)C>CN(C=O)C.CO>[CH:24]([OH:26])=[O:25].[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]([CH2:38][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

8

Reactant 5

HCID 5238Sodium IodideHCID 2424061-Chloro-3-(2-methylpropane-2-sulfonyl)propane2×HCID 516892Sodium BicarbonateHCID 434445061-Bromo-3-(2-methylpropane-2-sulfonyl)propaneHCID 579260486-Butyl-8-(4-piperidinyloxy)quinoline2×

Product 1

HCID 1317286526-Butyl-8-[(1-{3-[(1,1-di methylethyl)sulfonyl]propyl}-4-piperidinyl)oxy]quinoline, formate saltYield 40%

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) (28 mg, 0.10 mmol), sodium iodide (34 mg, 0.23 mmol) and sodium bicarbonate (60 mg, 0.7 mmol) was treated with a mixture of 3-bromopropyl 1,1-dimethylethyl sulfone and 3-chloropropyl 1,1-dimethylethyl sulfone (for example, as prepared for Intermediate 17) (1:1, 40 mg) in DMF (1.5 ml) and heated to 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 was purified by MDAP to give the title compound (20 mg, 40%): LCMS RT=2.76 min, ES+ve m/z 447 (M+H)+; 1H NMR δ (CD3OD) 8.78 (1H, dd, J=4, 2 Hz), 8.44 (1.6H, s), 8.24 (1H, dd, J=8, 2 Hz), 7.52 (1H, dd, J=8, 4 Hz), 7.32 (1H, br s), 7.19 (1H, br s), 5.03-4.96 (1H, m), 3.68-3.59 (2H, m), 3.40-3.26 (4H, obscured by CD3OD), 3.22 (2H, t, J=7 Hz), 2.79 (2H, t, J=7 Hz), 2.35-2.21 (6H, m), 1.75-1.67 (2H, m), 1.45-1.35 (2H, m), 1.40 (9H, s), 0.96 (3H, t, J=7 Hz).

Workup

  1. washeluted with methanol
  2. customfollowed by 10% aqueous 0.88 s
  3. concentrationconcentrated in vacuo
  4. customthe residue was purified by MDAP

Sources & evidence

ORD record
ord-75b0993cf97249f3b128f62560f0b6a6
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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