2-Bromo-1-[4-benzyloxy-3-[(dimethylsulfamoyl)amino]phenyl]ethanone → (+/-)-N'-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]-2-benzyloxyphenyl]-N,N-dimethylsulfamide Hydrochloride

HRID 635419Notes

Reaction equation

HRID 635419 reaction equation
[CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[S:6][C:5]=2[CH:4]=[C:3]([O:14][CH2:15][CH2:16][NH2:17])[CH:2]=1.Br[CH2:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[C:24]([NH:36][S:37](=[O:42])(=[O:41])[N:38]([CH3:40])[CH3:39])[CH:23]=1)=[O:21].CO.C(Cl)(Cl)[Cl:46].Cl.C(O)C>C(#N)C>[ClH:46].[CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[S:6][C:5]=2[CH:4]=[C:3]([O:14][CH2:15][CH2:16][NH:17][CH2:19][CH:20]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[C:24]([NH:36][S:37]([N:38]([CH3:39])[CH3:40])(=[O:42])=[O:41])[CH:23]=2)[OH:21])[CH:2]=1

Participants

6

Reactant 4

HCID 186151022-Bromo-1-[4-benzyloxy-3-[(dimethylsulfamoyl)amino]phenyl]ethanoneHCID 186151802-(Dibenzothiophen-3-yloxy)ethylamineHCID 21584188Chloroform methanolHCID 21887872Ethanol hydrochloride

Product 1

HCID 18615080(+/-)-N'-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]-2-benzyloxyphenyl]-N,N-dimethylsulfamide Hydrochloride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 462 mg of Intermediate 39 in 20 ml of anhydrous acetonitrile, a solution of 470 mg of Intermediate 40 in 10 ml of anhydrous acetonitrile was added under argon atmosphere at 0° C., whereupon the reaction mixture was removed from the ice bath and was agitated for 110 minutes. Thereto was then added a solution of 215 mg of sodium borohydride in 20 ml of absolute ethanol at room temperature. After agitation for 70 minutes, the reaction was terminated using 1 N hydrochloric acid (pH 4) and the thereto was added 0.54 g of ethanolamine. After agitation for 10 minutes, the mixture was diluted with ethyl acetate, organic layer was rinsed with saturated aqueous sodium chloride solution and dried, whereupon it was evaporated under a reduced pressure, whereby a crude product was obtained. This was purified by a column chromatography (methanol/chloroform of 3/100), whereby 200.2 mg of free amine product of the above-identified compound were obtained. Rf=0.37 (methanol/chloroform of 1/10). The procedures of adding thereto 1.1 equivalent amount of 0.1 N hydrogen chloride/ethanol to convert it into hydrochloride salt (the above-identified compound), distilling off of the solvent under a reduced pressure, adding to the resulting residue diethyl ether and filtering off the thereby deposited precipitate were repeated twice, followed by drying under a reduced pressure, whereby 210.8 mg of the above-identified compound were obtained.

Workup

  1. customwas removed from the ice bath
  2. additionThereto was then added a solution of 215 mg of sodium borohydride in 20 ml of absolute ethanol at room temperature
  3. waitAfter agitation for 70 minutes
  4. customthe reaction was terminated
  5. additionthe thereto was added 0.54 g of ethanolamine
  6. waitAfter agitation for 10 minutes
  7. additionthe mixture was diluted with ethyl acetate, organic layer
  8. washwas rinsed with saturated aqueous sodium chloride solution
  9. customdried, whereupon it
  10. customwas evaporated under a reduced pressure, whereby a crude product
  11. customwas obtained
  12. customThis was purified by a column chromatography (methanol/chloroform of 3/100), whereby 200.2 mg of free amine product of the above-identified compound
  13. customwere obtained
  14. additionThe procedures of adding
  15. distillationdistilling off of the solvent under a reduced pressure
  16. additionadding to the resulting residue diethyl ether
  17. filtrationfiltering off the
  18. customby drying under a reduced pressure

Sources & evidence

ORD record
ord-576c16a437cf410d937e5aeed855893e
Source dataset
uspto-grants-2001_02
Patent number
US06187809B1

Reaction notes

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