1-Hydroxybenzotriazole → HCID 57756836, Verbindung

HRID 228049Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 228049
[C:1]([C:4]12[CH2:11][CH2:10][C:7]([NH:12][CH2:13][C:14]([N:16]3[CH2:20][C@@H:19]([F:21])[CH2:18][C@H:17]3[C:22]#[N:23])=[O:15])([CH2:8][CH2:9]1)[CH2:6][CH2:5]2)(O)=[O:2].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[F:47][CH2:48][C@@H:49]([NH2:51])[CH3:50]>ClCCl.O.C(N(CC)CC)C>[F:21][C@@H:19]1[CH2:20][N:16]([C:14](=[O:15])[CH2:13][NH:12][C:7]23[CH2:6][CH2:5][C:4]([C:1]([NH:51][C@@H:49]([CH3:50])[CH2:48][F:47])=[O:2])([CH2:11][CH2:10]2)[CH2:9][CH2:8]3)[C@H:17]([C:22]#[N:23])[CH2:18]1

Komponenten

8

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11851333(2S)-1-fluoropropan-2-amine hydrochlorideHCID 57634365(2S,4S)-1-[[N-(4-carboxybicyclo[2,2,2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Produkt 1

HCID 57756836HCID 57756836, VerbindungAusbeute 31,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

(2S,4S)-1-[[N-(4-Carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (100 mg) and 1-hydroxybenzotriazole (61.5 mg) were dissolved in dichloromethane (4 mL). While this solution was chilled in an ice bath, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (119 mg) was added and the mixture was stirred at room temperature for 1 hour. Subsequently, a mixture of (2S)-1-fluoro-2-propylamine hydrochloride (32.0 mg), triethylamine (56.0 μL) and dichloromethane (2 mL) was added and the resulting mixture was stirred at room temperature for further 8 hours. Following addition of water, the dichloromethane layer was collected. The dichloromethane layer washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by a silica gel column (eluant:dichloromethane:methanol=10:1) to give (2S,4S)-4-fluoro-1-[[N-(4-[N-[(2S)-1-fluoro-2-propyl]amino]carbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (34.0 mg) as a white powder.

Aufarbeitung

  1. temperatureWhile this solution was chilled in an ice bath
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature for further 8 hours
  4. customthe dichloromethane layer was collected
  5. washThe dichloromethane layer washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by a silica gel column (eluant:dichloromethane:methanol=10:1)

Quellen und Nachweise

ORD-Eintrag
ord-3c3eacb47ef1415db3819b684e1bb8de
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07560569B2

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