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1,2-Dichloroethane → 4-[(S)-4-tert-Butoxycarbonyl-2-({4-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

HRID 1185431
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1185431
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][CH2:37][C:38]([OH:40])=O)[C:33]3[C:28](=[CH:29][C:30]([CH3:41])=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(Cl)CCl.FC1C(O)=C(F)C(F)=C(F)C=1F.FC(F)(F)C(O)=O.[CH:66]1([NH:70][C:71]([C@@H:73]2[CH2:77][CH2:76][CH2:75][NH:74]2)=[O:72])[CH2:69][CH2:68][CH2:67]1>CN(C=O)C.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:42])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][CH2:37][C:38]([N:74]3[CH2:75][CH2:76][CH2:77][C@H:73]3[C:71](=[O:72])[NH:70][CH:66]3[CH2:67][CH2:68][CH2:69]3)=[O:40])[C:33]3[C:28](=[CH:29][C:30]([CH3:41])=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]
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Komponenten

7

Edukt 4

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 68599196(S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetateHCID 685997964-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-7-methyl-quinoline-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester

Produkt 1

HCID 68598863
4-[(S)-4-tert-Butoxycarbonyl-2-({4-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a solution of 3.5 g of 4-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-7-methyl-quinoline-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester in 30 ml of DMF, 1.1 g of EDC, 1.1 g of pentafluorophenol and 1.8 g of NEM was added and the reaction mixture was warmed to 40° C. for 4 h. Then, after cooling to RT 2.6 g of (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetate and 1 g of NEM in 10 ml of DMF was added. After 4 h the reaction mixture was diluted with water and extracted with DCM (3×150 ml). The combined organic phases were dried over MgSO4 and the solvents were removed under reduced pressure. The crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 1.8 g.

Aufarbeitung

  1. additionwas added
  2. extractionextracted with DCM (3×150 ml)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. customthe solvents were removed under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate
  6. additionThe fractions containing the product
  7. customthe solvent evaporated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-f4f08340426242878470bc62e471877e
Quelldatensatz
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08669266B2

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