Methanesulfonyl chloride → n-[1-[3-(4-Fluorophenyl)propan-1-yl]-piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide

HRID 1978484Notes

Reaction equation

HRID 1978484 reaction equation
CS(Cl)(=O)=O.[F:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][CH2:15]O)=[CH:9][CH:8]=1.C(=O)([O-])O.[Na+].Cl.Cl.[NH:24]1[CH2:29][CH2:28][CH:27]([NH:30][C:31]([C:33]2[S:43][C:42]3[N:44]4[C:35](=[CH:36][N:37]=[C:38]4[CH:39]=[CH:40][CH:41]=3)[CH:34]=2)=[O:32])[CH2:26][CH2:25]1.S([O-])(=O)(=O)C>C(OCC)C.C(O)C.O.C(N(CC)CC)C>[F:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][CH2:14][CH2:15][N:24]2[CH2:25][CH2:26][CH:27]([NH:30][C:31]([C:33]3[S:43][C:42]4[N:44]5[C:35](=[CH:36][N:37]=[C:38]5[CH:39]=[CH:40][CH:41]=4)[CH:34]=3)=[O:32])[CH2:28][CH2:29]2)=[CH:11][CH:12]=1

Participants

10

Reactant 5

HCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 516892Sodium BicarbonateHCID 137472413-(4-Fluorophenyl)propan-1-olHCID 21994154N-(piperidin-4-yl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride

Product 1

HCID 21993793n-[1-[3-(4-Fluorophenyl)propan-1-yl]-piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8471TriethylamineSolvent2×

Procedure

Under nitrogen gas, 0.47 ml (6.07 mM) of methane-sulfonyl chloride was added to a solution of 0.62 g (4.02 mM) of 3-(4-fluorophenyl)propanol and 1.1 ml (7.89 mM) of triethylamine in diethyl ether (8 ml) at 0° C. and the mixture was stirred at the prevailing temperature for 1 hour. The reaction was stopped by adding saturated aqueous solution of sodium hydrogen carbonate and the reaction mixture was extracted with diethyl ether. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over MgSO4. The solvent was then distilled off under reduced pressure to recover the crude mesylate. This crude product was not purified but used as it was in the next reaction. To a solution of 0.75 g (2.00 mM) of N-(piperidin-4-yl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride and 1.4 ml (10.0 mM) of triethylamine in ethanol (8 ml) was added 0.94 g (<4.02 mM) of the above crude mesylate at room temperature and the mixture was refluxed under nitrogen for 16 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride, dried over MgSO4, and concentrated. The crude product thus obtained was purified by column chromatography (methanol/ethyl acetate 20-30-40%) and recrystallization from ethyl acetate-ethanol to provide the title compound as red-purple crystals.

Workup

  1. extractionthe reaction mixture was extracted with diethyl ether
  2. washThe organic layer was washed with saturated aqueous solution of sodium chloride
  3. dry with materialdried over MgSO4
  4. distillationThe solvent was then distilled off under reduced pressure
  5. customto recover the crude mesylate
  6. customThis crude product was not purified
  7. customwas in the next reaction
  8. temperaturethe mixture was refluxed under nitrogen for 16 hours
  9. temperatureAfter cooling
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with saturated aqueous solution of sodium chloride
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated
  14. customThe crude product thus obtained
  15. customwas purified by column chromatography (methanol/ethyl acetate 20-30-40%) and recrystallization from ethyl acetate-ethanol

Sources & evidence

ORD record
ord-2f27dfe0b20c4ba1886f9f937125eaf8
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

Loading…