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

HRID 412087

반응식

HRID 412087 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b5f9a0875f9d49ae92ab97c410c03b7a
출처 데이터셋
uspto-grants-2003_05
특허 번호
US06562842B2

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