Hydrochloric Acid → 4-[[(1R)-3-(4-morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-nitroBenzenesulfonamide

HRID 1476307Notes

Reaction equation

HRID 1476307 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7](=O)[CH2:8][C@@H:9]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:27])=[O:26])=[CH:21][C:20]=2[N+:29]([O-:31])=[O:30])[CH2:10][S:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:3][CH2:2]1.B.C1COCC1.Cl.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.CO>[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][C@@H:9]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:26])=[O:27])=[CH:21][C:20]=2[N+:29]([O-:31])=[O:30])[CH2:10][S:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 2723981Borane;tetrahydrofuranHCID 11591105(R)-4-(4-morpholino-4-oxo-1-(phenylthio)butan-2-ylamino)-3-nitrobenzenesulfonamide2×

Product 1

HCID 117054054-[[(1R)-3-(4-morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-nitroBenzenesulfonamideYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-4-(4-Morpholino-4-oxo-1-(phenylthio)butan-2-ylamino)-3-nitrobenzenesulfonamide (INTERMEDIATE 73, 523.6 mg, 1.09 mmol) was dissolved under a nitrogen atmosphere in a solution of borane-THF complex (1M in THF; 2.4 ml, 2.4 mmol) and the resulting solution was stirred at room temperature overnight. The flask was opened to atmosphere and cautiously treated with MeOH (1.20 ml) followed by concentrated HCl (0.48 ml). The resulting mixture was heated at reflux for 3 hours and was then allowed to cool to room temperature. The pH of the mixture was adjusted to approximately 10 by the addition of aqueous solution of Na2CO3 (4 M) resulting in a precipitate. The mixture was dissolved in EtOAc (75 ml) and washed with water (40 ml), brine (40 ml), and dried (Na2SO4). Evaporation of the volatiles under reduced pressure afforded a concentrate, which was purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes) to provide the title product (406.6 mg, yield: 80%).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 3 hours
  3. temperatureto cool to room temperature
  4. customresulting in a precipitate
  5. washwashed with water (40 ml), brine (40 ml)
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of the volatiles under reduced pressure
  8. customafforded a concentrate, which
  9. customwas purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d8c22b4605bb45afbb69b6e08126a384
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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