反応 #499269

反応方程式

Cbz-leucine

EDCI

HOBT

1,3-diamino-propan-2-ol

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

N-methyl morpholine

→

title compound

収率 2.0%

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

収率 2.0%

溶媒

DMF

反応条件

後処理

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe reaction was stirred 3 h at RT
3. 3
   その他The reaction was partitioned between water and EtOAc
4. 4
   乾燥the combined organics were dried with magnesium sulfate
5. 5
   濃縮concentrated 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
   その他The excess Jones reagent was then quenched with isopropanol (1.0 ml)
10. 10
    workup.ADDITIONthe reaction was diluted with EtOAc (20 ml)
11. 11
    抽出was extracted with water (2×20 ml)
12. 12
    その他to remove the inorganic salts
13. 13
    乾燥The combined organics were dried with magnesium sulfate
14. 14
    ろ過filtered
15. 15
    濃縮concentrated
16. 16
    その他chromatographed (silica gel, 2-5% MeOH/methylene chloride)
17. 17
    その他the product was triturated from methylene chloride

実験手順

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.

出典