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

HRID 1476302노트

반응식

HRID 1476302 반응식
[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

참가 물질

7

반응물 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 acid2회

생성물 1

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

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매2회HCID 31374Dimethylacetamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-0e04ea262db24c5e9f97eee167b95611
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018381B2

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