Hydrochloric Acid → 4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1476316Notes

Reaction equation

HRID 1476316 reaction equation
[CH2:1]([N:3]([CH2:6][C@@H:7]1[N:12]([C:13](=O)[CH2:14][C@@H:15]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([S:31]([NH2:34])(=[O:33])=[O:32])=[CH:27][C:26]=2[S:35]([C:38]([F:41])([F:40])[F:39])(=[O:37])=[O:36])[CH2:16][S:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:11][CH2:10][O:9][CH2:8]1)[CH2:4][CH3:5])[CH3:2].C1COCC1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.CO>[CH2:1]([N:3]([CH2:6][C@@H:7]1[N:12]([CH2:13][CH2:14][C@@H:15]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([S:31]([NH2:34])(=[O:32])=[O:33])=[CH:27][C:26]=2[S:35]([C:38]([F:40])([F:39])[F:41])(=[O:37])=[O:36])[CH2:16][S:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:11][CH2:10][O:9][CH2:8]1)[CH2:4][CH3:5])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 667236584-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×

Product 1

HCID 667234924-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideYield 37%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 87, 360 mg, 0.55 mmol) and 1 M borane-tetrahydrofuran complex in THF (1191 μl, 1.19 mmol) was stirred at room temperature for 16 hours. The reaction mixture was treated carefully with MeOH (5 ml) and concentrated HCl (1 ml). The mixture was heated at 80° C. for 3 hours, cooled to r.t, and the pH was adjusted to pH 10 with 4 N aqueous sodium carbonate. The mixture was diluted with ethyl acetate (300 ml), washed successively with water (150 ml) and brine (150 ml), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0→20% MeOH/DCM over 15 minutes) to give the title product (130 mg, yield: 37%).

Workup

  1. temperatureThe mixture was heated at 80° C. for 3 hours
  2. temperaturecooled
  3. washwashed successively with water (150 ml) and brine (150 ml)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe concentrate was purified by column chromatography (ISCO, eluting with 0→20% MeOH/DCM over 15 minutes)

Sources & evidence

ORD record
ord-eb78eecc49544415a185b5e9517d30df
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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