Morpholine → 4-[[(1R)-3-(4-Morpholinyl)-3-oxo-1-[(phenylthio)methyl]propyl]amino]-3-trifluoromethylsulfonyl-benzenesulfonamide

HRID 1771199Notes

Reaction equation

HRID 1771199 reaction equation
[C:1]1([S:7][CH2:8][C@H:9]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21](=[O:24])(=[O:23])[NH2:22])=[CH:17][C:16]=2[S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[CH2:10][C:11](O)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1.CCN(C(C)C)C(C)C>CC(N(C)C)=O.CCOC(C)=O>[O:59]1[CH2:60][CH2:61][N:56]([C:11](=[O:12])[CH2:10][C@@H:9]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([NH2:22])(=[O:24])=[O:23])=[CH:17][C:16]=2[S:25]([C:28]([F:31])([F:29])[F:30])(=[O:27])=[O:26])[CH2:8][S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:57][CH2:58]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66723519(R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid2×

Product 1

HCID 667238584-[[(1R)-3-(4-Morpholinyl)-3-oxo-1-[(phenylthio)methyl]propyl]amino]-3-trifluoromethylsulfonyl-benzenesulfonamideYield 89%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

A solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino) butanoic acid (INTERMEDIATE 8, 1.99 g, 4.01 mmol) and HATU (1.83 g, 4.82 mmol) in DMA (18.0 ml) was treated with morpholine (0.35 ml, 4.02 mmol) and DIPEA (1.40 ml, 8.02 mmol). The resulting reaction mixture was stirred at room temperature for 1 hour and then diluted with EtOAc (250 ml). The organic layer was washed with water (3×250 ml), 1M aq. NaHSO4 (200 ml), and saturated aq. NaHCO3 (200 ml). The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure to provide a sticky foam. The foam was dissolved in EtOAc (40 ml) and washed with water (2×250 ml). During the second wash material precipitated. EtOAc (80 ml) was added and the resulting mixture was shaken, resulting in redissolution of the precipitate. The mixture was further dried (Na2SO4), filtered, and evaporated under reduced pressure. The residue was dissolved in a few ml of DCM resulting in the formation of a precipitate. Finally, evaporation of the volatiles under reduced pressure afforded the title product (2.02 g, yield: 89%).

Workup

  1. customThe resulting reaction mixture
  2. washThe organic layer was washed with water (3×250 ml), 1M aq. NaHSO4 (200 ml), and saturated aq. NaHCO3 (200 ml)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customto provide a sticky foam
  7. washwashed with water (2×250 ml)
  8. customDuring the second wash material precipitated
  9. additionEtOAc (80 ml) was added
  10. stirringthe resulting mixture was shaken
  11. customresulting in redissolution of the precipitate
  12. dry with materialThe mixture was further dried (Na2SO4)
  13. filtrationfiltered
  14. customevaporated under reduced pressure
  15. dissolutionThe residue was dissolved in a few ml of DCM resulting in the formation of a precipitate
  16. customFinally, evaporation of the volatiles under reduced pressure

Sources & evidence

ORD record
ord-86a31eeeadf248c0a1d0168c070ba374
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

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