Diisopropylethylamine → (Z)-N-[2-[[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]phenyl]amino]-2-oxoethyl]-4-(fluorosulfonyl)benzamide

HRID 382042Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 382042
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2/[C:10](=[CH:18]/[C:19]2[NH:20][CH:21]=[CH:22][CH:23]=2)/[C:11](=[O:17])[NH:12]3)[CH:5]=[CH:6][CH:7]=1.[F:24][S:25]([C:28]1[CH:40]=[CH:39][C:31]([C:32]([NH:34][CH2:35][C:36](O)=[O:37])=[O:33])=[CH:30][CH:29]=1)(=[O:27])=[O:26].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[O:17]=[C:11]1[NH:12][C:13]2[C:9](/[C:10]/1=[CH:18]/[C:19]1[NH:20][CH:21]=[CH:22][CH:23]=1)=[C:8]([C:4]1[CH:3]=[C:2]([NH:1][C:36](=[O:37])[CH2:35][NH:34][C:32](=[O:33])[C:31]3[CH:30]=[CH:29][C:28]([S:25]([F:24])(=[O:27])=[O:26])=[CH:40][CH:39]=3)[CH:7]=[CH:6][CH:5]=1)[CH:16]=[CH:15][CH:14]=2

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 9819193(Z)-4-(3-aminophenyl)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-oneHCID 183638592-{[4-(Fluorosulfonyl)phenyl]formamido}acetic acid

Produkt 1

HCID 59971433(Z)-N-[2-[[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]phenyl]amino]-2-oxoethyl]-4-(fluorosulfonyl)benzamideAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of (Z)-4-(3-aminophenyl)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one (30 mg, 0.100 mmol) (from Example 4 supra), crude (4-fluorosulfonyl-benzoylamino)-acetic acid (28 mg, 0.107 mmol) (from step B above), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 45 mg, 0.119 mmol) (Advance ChemTech), 1-hydroxybenzotriazole hydrate (HOBT, 16 mg, 0.118 mmol) (Aldrich), and N,N-diisopropylethylamine (52 μL, 0.300 mmol) (Aldrich) in 3 mL of dry N,N-dimethylformamide (Fisher Scientific) was stirred at 50° C. under a nitrogen atmosphere for 7 h then stirred at room temperature under a nitrogen atmosphere for 12 h. The reaction mixture was diluted with 40 mL ethyl acetate and washed with distilled water. The organic phase was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 40% acetone-hexanes then 70% acetone-hexanes elution) provided pure (Z)-N-[2-[[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]phenyl]amino]-2-oxoethyl]-4-(fluorosulfonyl)benzamide (yield: 13 mg, 24%) as a yellow solid (mp 248-250° C.).

Aufarbeitung

  1. washwashed with distilled water
  2. concentrationThe organic phase was concentrated in vacuo
  3. washFlash chromatography (Merck Silica gel 60, 230-400 mesh, 40% acetone-hexanes then 70% acetone-hexanes elution)

Quellen und Nachweise

ORD-Eintrag
ord-5c969d28323e4a879ddebce156cbc5fb
Quelldatensatz
uspto-grants-2001_10
Patentnummer
US06307056B1

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