Methanol → HCID 25190257, compound

HRID 1363025Notes

Reaction equation

HRID 1363025 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].[S:22]1(=[O:28])(=[O:27])[CH:26]=[CH:25][CH2:24][CH2:23]1.CO>C1COCC1>[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]([CH:24]4[CH2:25][CH2:26][S:22](=[O:28])(=[O:27])[CH2:23]4)[CH2:20][CH2:21]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 887MethanolHCID 14497Thiophene, 2,3-dihydro-, 1,1-dioxide2×HCID 579260486-Butyl-8-(4-piperidinyloxy)quinoline2×

Product 1

HCID 25190257HCID 25190257, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-butyl-8-(4-piperidinyloxy)quinoline (for example, as prepared for Intermediate 4) (0.15 g, 0.53 mmol) in THF (5 ml) was added 2,3-dihydrothiophene 1,1-dioxide (commercially available, for example, from AKOS) (0.150 g, 1.27 mmol). The solution was heated to 80° C. for 2.5 h. To the solution at ambient temperature was added a further amount of 2,3-dihydrothiophene 1,1-dioxide (0.150 g, 1.27 mmol) and the solution stirred overnight at ambient temperature. The solution was heated to reflux for 2 h and then at ambient temperature for 7 days. The reaction was applied to an SCX-2 cartridge (20 g), preconditioned with methanol, and the cartridge washed with methanol (2 column volumes). The cartridge was eluted with 10% 0.880 s.g. ammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo. The residue was purified by MDAP and the appropriate fractions combined and evaporated. The combined fractions were applied to an SCX-2 cartridge (20 g), preconditioned with methanol, and the cartridge washed with methanol. The cartridge was eluted with 10% 0.88 s.g. ammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo to give the title compound (17 mg, 8%). LCMS RT=2.59 min, ES+ve m/z 403 (M+H)+.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 2 h
  3. waitat ambient temperature for 7 days
  4. washthe cartridge washed with methanol (2 column volumes)
  5. washThe cartridge was eluted with 10% 0.880 s
  6. concentrationammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo
  7. customThe residue was purified by MDAP
  8. customevaporated
  9. washthe cartridge washed with methanol
  10. washThe cartridge was eluted with 10% 0.88 s
  11. concentrationammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo

Sources & evidence

ORD record
ord-65c1ad7e021c47afa74383afe74b235a
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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