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Diisopropylethylamine → tert-Butyl 1-(3-{[4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoyl]amino}benzyl)cyclopropanecarboxylate

HRID 877257
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 877257
[NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1.[F:19][C:20]([F:46])([F:45])[CH:21]([CH3:44])[CH:22]([C:26]1[CH:31]=[CH:30][C:29]([CH2:32][N:33]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][C:39]=3[F:42])[C:34]2=[O:43])=[CH:28][CH:27]=1)[C:23](O)=[O:24].O.ON1C2C=CC=CC=2N=N1.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>CN(C=O)C.O>[F:46][C:20]([F:19])([F:45])[CH:21]([CH3:44])[CH:22]([C:26]1[CH:27]=[CH:28][C:29]([CH2:32][N:33]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][C:39]=3[F:42])[C:34]2=[O:43])=[CH:30][CH:31]=1)[C:23]([NH:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:13])[CH3:14])=[O:10])[CH2:8][CH2:7]1)=[O:24]
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Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136514tert-Butyl 1-(3-aminobenzyl)cyclopropanecarboxylateHCID 581367454,4,4-Trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid

Produkt 1

HCID 58136669tert-Butyl 1-(3-{[4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoyl]amino}benzyl)cyclopropanecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

110.8 mg (0.41 mmol) of tert-butyl 1-(3-aminobenzyl)cyclopropanecarboxylate were added to a solution of 129.0 mg (0.33 mmol) of 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid and 52.9 mg (0.39 mmol) of 1-hydroxy-1H-benzotriazole hydrate in 1 ml of DMF. At 0° C., 142 μl (0.82 mmol) of DIEA and then, a little at a time, 136.5 mg (0.36 mmol) of HATU were added to the resulting mixture. The reaction mixture was then slowly warmed to RT and stirred at RT for 2.5 h. The mixture was added to water and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient). This gave 97.4 mg (47.6% of theory) of the title compound.

Aufarbeitung

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe combined organic phases were dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient)

Quellen und Nachweise

ORD-Eintrag
ord-4c38c5f9bc584aaf9d83229306163b46
Quelldatensatz
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08987256B2

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