4-Methylmorpholine → 1-(Cbz-leucinyl)-amino-3-(4-(3chloro-2-cyano-phenoxy)-phenyl sulfonamido)-propan-2-one

HRID 2270464

Reaktionsgleichung

Reaktionsgleichung von HRID 2270464
[C:1]([NH:11][C@H:12]([C:17]([OH:19])=O)[CH2:13][CH:14]([CH3:16])[CH3:15])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:41][CH2:42][CH:43]([OH:46])[CH2:44][NH2:45].CN1CCOCC1.[Cl:54][C:55]1[C:56]([C:72]#[N:73])=[C:57]([CH:69]=[CH:70][CH:71]=1)[O:58][C:59]1[CH:64]=[CH:63][C:62]([S:65](Cl)(=[O:67])=[O:66])=[CH:61][CH:60]=1>CN(C=O)C>[C:1]([NH:11][C@H:12]([C:17]([CH:42]([NH2:41])[C:43](=[O:46])[CH2:44][NH:45][S:65]([C:62]1[CH:61]=[CH:60][C:59]([O:58][C:57]2[CH:69]=[CH:70][CH:71]=[C:55]([Cl:54])[C:56]=2[C:72]#[N:73])=[CH:64][CH:63]=1)(=[O:66])=[O:67])=[O:19])[CH2:13][CH:14]([CH3:15])[CH3:16])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Komponenten

8

Edukt 6

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 611571,3-Diamino-2-propanolHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 757711-HydroxybenzotriazoleHCID 27769174-(3-Chloro-2-cyanophenoxy)benzenesulfonyl chloride

Produkt 1

HCID 696122931-(Cbz-leucinyl)-amino-3-(4-(3chloro-2-cyano-phenoxy)-phenyl sulfonamido)-propan-2-oneAusbeute 2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Cbz-leucine (660 mg, 25 mmol), EDCI (480 mg, 2.5 mmol), HOBT (340 mg, 2.5 mmol) was dissolved in DMF (10 ml) with 1,3 diamino-propan-2-ol (225 mg, 2.5 mmol) and was stirred at RT overnight. N-methyl morpholine (0.41 ml, 3.75 mmol) was added followed by 4-(3-Chloro-2-cyano-phenoxy)-phenyl sulfonyl chloride (820 mg, 2.5 mmol, Maybridge) was added and the reaction was stirred 3 h at RT. The reaction was partitioned between water and EtOAc and the combined organics were dried with magnesium sulfate, then concentrated in vacuo. The crude 1-(Cbz-leucinyl)amino-3-(4(3-chloro-2-cyano-phenoxy)-phenyl sulfonamido)-propan-2-ol was then dissolved in acetone (5.0 ml) and Jones reagent (3.0 ml, 1.5 M) was added dropwise, and the reaction was stirred overnight at RT. The excess Jones reagent was then quenched with isopropanol (1.0 ml), then the reaction was diluted with EtOAc (20 ml) and was extracted with water (2×20 ml) to remove the inorganic salts. The combined organics were dried with magnesium sulfate, filtered, concentrated, and chromatographed (silica gel, 2-5% MeOH/methylene chloride), then the product was triturated from methylene chloride to give the title compound as a white solid (26 mg, 2%). MS(ES) M+H+=627.

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction was stirred 3 h at RT
  3. customThe reaction was partitioned between water and EtOAc
  4. dry with materialthe combined organics were dried with magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude 1-(Cbz-leucinyl)amino-3-(4(3-chloro-2-cyano-phenoxy)-phenyl sulfonamido)-propan-2-ol was then dissolved in acetone (5.0 ml)
  7. additionJones reagent (3.0 ml, 1.5 M) was added dropwise
  8. stirringthe reaction was stirred overnight at RT
  9. customThe excess Jones reagent was then quenched with isopropanol (1.0 ml)
  10. additionthe reaction was diluted with EtOAc (20 ml)
  11. extractionwas extracted with water (2×20 ml)
  12. customto remove the inorganic salts
  13. dry with materialThe combined organics were dried with magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customchromatographed (silica gel, 2-5% MeOH/methylene chloride)
  17. customthe product was triturated from methylene chloride

Quellen und Nachweise

ORD-Eintrag
ord-780160ff58634bf4b2b2e46a12426ff9
Quelldatensatz
uspto-grants-2001_12
Patentnummer
US06331542B1

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