Hydrochloric Acid → 4-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide

HRID 1919542Notes

Reaction equation

HRID 1919542 reaction equation
[N:1]1([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[S:29]([C:32]([F:35])([F:34])[F:33])(=[O:31])=[O:30])[CH2:10][S:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CO.Cl>O1CCCC1>[N:1]1([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[S:29]([C:32]([F:33])([F:34])[F:35])(=[O:30])=[O:31])[CH2:10][S:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 667238584-[[(1R)-3-(4-Morpholinyl)-3-oxo-1-[(phenylthio)methyl]propyl]amino]-3-trifluoromethylsulfonyl-benzenesulfonamide

Product 1

HCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamideYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

Borane tetrahydrofuran complex (4.21 mmol) was added dropwise over 2 h to the amide intermediate c (1.24 mmol) in tetrahydrofuran (10 ml) at room temperature under a nitrogen atmosphere. The solution was then stirred at 55° C. for 24 h. The solution was cooled to 0° C. and treated with methanol (2 ml). To this mixture was added concentrated hydrochloric acid (0.5 ml) and the solution heated at 65° C. for 10 h. The solution was then concentrated in vacuo and poured into a 2 N sodium hydroxide solution (10 ml). The aqueous layer was then extracted with ethyl acetate (2×10 ml), the organic layer was dried (MgSO4) and concentrated in vacuo. The resulting residue was applied to silica chromatography gradient eluting with 100% dichloromethane to 10% methanol/dichloromethane to yield intermediate 4-((R)-3-morpholin-4-yl-1-phenylsulfanylmethyl-propylamino)-3-trifluoromethanesulfonyl-benzenesulfonamide, 4-((R)-3-morpholin-4-yl-1-phenylsulfanylmethyl-propylamino)-3-trifluoromethanesulfonyl-benzenesulfonamide as a white solid (76%). 1H NMR (300 MHz, DMSO) δ 7.97 (1H, d, J 2.2 Hz), 7.83 (1H, dd, J 9.2 and 2.3 Hz), 7.35-7.26 (6H, m, ArH), 7.20 (1H, tt, J 7.0 and 1.8 Hz), 7.04 (1H, d, J 9.6 Hz), 6.89 (1H, bd, J 9.1 Hz), 4.12-4.02 (1H, m), 3.49 (4H, bs), 3.37-3.22 (2H, m), 2.33-2.14 (6H, m), 1.94-1.88 (1H, m), 1.76-1.70 (1H, m).

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. temperaturethe solution heated at 65° C. for 10 h
  3. concentrationThe solution was then concentrated in vacuo
  4. additionpoured into a 2 N sodium hydroxide solution (10 ml)
  5. extractionThe aqueous layer was then extracted with ethyl acetate (2×10 ml)
  6. dry with materialthe organic layer was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. washeluting with 100% dichloromethane to 10% methanol/dichloromethane

Sources & evidence

ORD record
ord-b7bff0467528446bbfc97012e22f60d0
Source dataset
uspto-grants-2012_05
Patent number
US08168645B2

Reaction notes

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