N-[3-(2-bromoacetyl)phenyl]methanesulfonamide → (+/-)-N-[3-[2-[2-(Dibenzothiophen-3-yloxy)ethlamino]-1-hydroxyethyl]phenyl]methanesulfonamide Hydrochloride

HRID 1265205Notes

Reaction equation

HRID 1265205 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][CH:25]=[C:24]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])[CH:23]=1)=[O:21].CO.C(OCC)(=O)C.[ClH:41].C(O)C>C(#N)C>[ClH:41].[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:23]=[C:24]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])[CH:25]=[CH:26][CH:27]=2)[OH:21])[CH:2]=1

Participants

6

Reactant 4

HCID 11346858N-[3-(2-bromoacetyl)phenyl]methanesulfonamideHCID 186151802-(Dibenzothiophen-3-yloxy)ethylamineHCID 21584119Ethylacetate methanolHCID 21887872Ethanol hydrochloride

Product 1

HCID 21258620(+/-)-N-[3-[2-[2-(Dibenzothiophen-3-yloxy)ethlamino]-1-hydroxyethyl]phenyl]methanesulfonamide 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 320.2 mg of Intermediate 14 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 115 minutes. To this mixture was then added a solution of 215 mg of sodium borohydride in 20 ml of absolute ethanol at room temperature. After agitation for 75 minutes, the reaction was terminated using 1 N hydrochloric acid (pH 4) and 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. This was purified by a column chromatography (elution by methanol/ethyl acetate of 1/7), whereby 251.3 mg of fractions containing the free amine product of the above-identified compound were obtained. This was further purified by a PTLC (elution with methanol/ethyl acetate of 1/7), whereby 134.7 mg of free amine product of the above-identified compound were obtained. Rf=0.50 (methanol/ethyl acetate of 1/7). To this, 1.1 equivalent amount of 0.1 N hydrogen chloride/ethanol were added to convert it into hydrochloride salt (the above-identified compound), which was washed with ethanol, ethyl acetate and diethyl ether, successively, with subsequent drying under a reduced pressure, whereby 93.9 mg of the above-identified compound were obtained.

Workup

  1. customwas removed from the ice bath
  2. additionTo this mixture was then added a solution of 215 mg of sodium borohydride in 20 ml of absolute ethanol at room temperature
  3. waitAfter agitation for 75 minutes
  4. customthe reaction was terminated
  5. additionwas 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
  11. customThis was purified by a column chromatography (elution by methanol/ethyl acetate of 1/7), whereby 251.3 mg of fractions
  12. additioncontaining the free amine product of the above-identified compound
  13. customwere obtained
  14. customThis was further purified by a PTLC (elution with methanol/ethyl acetate of 1/7), whereby 134.7 mg of free amine product of the above-identified compound
  15. customwere obtained
  16. washwas washed with ethanol, ethyl acetate and diethyl ether
  17. customsuccessively, with subsequent drying under a reduced pressure

Sources & evidence

ORD record
ord-edf16a7c385842b1a8f8c77007bea227
Source dataset
uspto-grants-2003_04
Patent number
US06545053B1

Reaction notes

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