Reacción #499269

Ecuación de reacción

Cbz-leucine

EDCI

HOBT

1,3-diamino-propan-2-ol

4-(3-Chloro-2-cyano-phenoxy)-phenyl sulfonyl chloride

N-methyl morpholine

→

title compound

Rendimiento 2.0%

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

Rendimiento 2.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe reaction was stirred 3 h at RT
3. 3
   OtroThe reaction was partitioned between water and EtOAc
4. 4
   Secadothe combined organics were dried with magnesium sulfate
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   workup.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. 7
   workup.ADDITIONJones reagent (3.0 ml, 1.5 M) was added dropwise
8. 8
   workup.STIRRINGthe reaction was stirred overnight at RT
9. 9
   OtroThe excess Jones reagent was then quenched with isopropanol (1.0 ml)
10. 10
    workup.ADDITIONthe reaction was diluted with EtOAc (20 ml)
11. 11
    Extracciónwas extracted with water (2×20 ml)
12. 12
    Otroto remove the inorganic salts
13. 13
    SecadoThe combined organics were dried with magnesium sulfate
14. 14
    Filtraciónfiltered
15. 15
    Concentraciónconcentrated
16. 16
    Otrochromatographed (silica gel, 2-5% MeOH/methylene chloride)
17. 17
    Otrothe product was triturated from methylene chloride

Procedimiento

Cbz-leucine (660 mg, 2.5 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.

Fuente