Diisopropylethylamine → (2S,4S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester

HRID 1481920Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1481920
[N:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:7])[C@H:2]([C:4]([OH:6])=O)[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH2:49]([O:56][C:57]([C@@H:59]1[CH2:63][C@H:62]([NH:64][C:65]([O:67][CH2:68][CH:69]2[C:81]3[CH:80]=[CH:79][CH:78]=[CH:77][C:76]=3[C:75]3[C:70]2=[CH:71][CH:72]=[CH:73][CH:74]=3)=[O:66])[CH2:61][N:60]1[C:82](=[O:91])[C@@H:83]([NH2:90])[CH:84]1[CH2:89][CH2:88][CH2:87][CH2:86][CH2:85]1)=[O:58])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>CN(C=O)C>[CH2:49]([O:56][C:57]([C@@H:59]1[CH2:63][C@H:62]([NH:64][C:65]([O:67][CH2:68][CH:69]2[C:81]3[CH:80]=[CH:79][CH:78]=[CH:77][C:76]=3[C:75]3[C:70]2=[CH:71][CH:72]=[CH:73][CH:74]=3)=[O:66])[CH2:61][N:60]1[C:82](=[O:91])[C@@H:83]([NH:90][C:4](=[O:6])[C@@H:2]([N:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH3:7])[CH3:3])[CH:84]1[CH2:89][CH2:88][CH2:87][CH2:86][CH2:85]1)=[O:58])[C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90220202(2S,4S)-1-((S)-2-amino-2-cyclohexyl-acetyl)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester hydrochloride

Produkt 1

HCID 90220266(2S,4S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl esterAusbeute 99,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of Boc-N-Me-Ala-OH (351 mg, 1.73 mmol) in DMF at 0° C. was added DIPEA (1.27 mL, 8.85 mmol) and HATU (626 mg, 1.65 mmol). After 30 min, (2S,4S)-1-((S)-2-amino-2-cyclohexyl-acetyl)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester hydrochloride (0.97 g, 1.57 mmol) was added, the cooling bath removed and the reaction stirred for 1 h. The mixture was diluted with ethyl acetate, washed with saturated ammonium chloride solution, saturated sodium bicarbonate solution, water, and brine and dried over anhydrous magnesium sulfate. Concentration gave (2S,4S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester (1.2 g) as an oil that was used without further purification or characterization.

Aufarbeitung

  1. customthe cooling bath removed
  2. additionThe mixture was diluted with ethyl acetate
  3. washwashed with saturated ammonium chloride solution, saturated sodium bicarbonate solution, water, and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationConcentration

Quellen und Nachweise

ORD-Eintrag
ord-e6662192416d41ff934040ca92d267bd
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409888B2

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