Diisopropylethylamine → N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]-4-fluoro-benzamide

HRID 2068554Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2068554
[CH:1]1[N:5]2[C:6]3[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=3[CH2:8][CH2:9][C@@H:10]([NH2:11])[C:4]2=[N:3][CH:2]=1.[F:16][C:17]1[CH:31]=[CH:30][C:20]([C:21]([NH:23][C:24]2([C:27](O)=[O:28])[CH2:26][CH2:25]2)=[O:22])=[CH:19][CH:18]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH:1]1[N:5]2[C:6]3[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=3[CH2:8][CH2:9][C@@H:10]([NH:11][C:27]([C:24]3([NH:23][C:21](=[O:22])[C:20]4[CH:30]=[CH:31][C:17]([F:16])=[CH:18][CH:19]=4)[CH2:26][CH2:25]3)=[O:28])[C:4]2=[N:3][CH:2]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58304055(R)-5,6-Dihydro-4H-benzo[F]imidazo[1,2-A]azepin-4-amineHCID 654532291-[(4-Fluorobenzoyl)amino]cyclopropanecarboxylic acid

Produkt 1

HCID 67233952N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]-4-fluoro-benzamideAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Combine (4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-amine (95.0 mg, 0.48 mmol), 1-[(4-fluorobenzoyl)amino]cyclopropanecarboxylic acid (128.0 mg, 0.57 mmol), and O—-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (218.0 mg, 0.57 mmol) in N,N-dimethylformamide (4 mL). Add diisopropylethylamine (0.21 mL, 1.19 mmol) and stir the reaction for approximately 16 hours at ambient temperature under nitrogen. Dilute the reaction with ethyl acetate, wash with saturated sodium bicarbonate and brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by flash chromatography (3% ammonia (2M) solution in methanol/dichloromethane) to give the title compound (131.0 mg, 68%): MS (m/z): 405 (M+1).

Aufarbeitung

  1. customthe reaction for approximately 16 hours at ambient temperature under nitrogen
  2. additionDilute
  3. washwash with saturated sodium bicarbonate and brine
  4. dry with materialdry over sodium sulfate
  5. concentrationconcentrate the organic layer under reduced pressure
  6. customPurify the residue by flash chromatography (3% ammonia (2M) solution in methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-08bbeb7bb91f4ef4a0e0df0bb84a9fbc
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08299061B2

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