2-Fluoroaniline → 4-chloro-2-fluoro-N-(2-fluorophenyl)-5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonamide

HRID 1951512Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1951512
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([S:12](Cl)(=[O:14])=[O:13])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH2:16]1[NH:21][CH2:20][CH2:19][N:18]2[CH2:22][CH2:23][CH2:24][C@@H:17]12.C(=O)([O-])[O-].[Na+].[Na+].[F:31][C:32]1[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=1[NH2:34]>ClCCl.CO>[Cl:1][C:2]1[C:3]([C:4]([N:21]2[CH2:20][CH2:19][N:18]3[CH2:22][CH2:23][CH2:24][C@H:17]3[CH2:16]2)=[O:5])=[CH:7][C:8]([S:12]([NH:34][C:33]2[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=2[F:31])(=[O:14])=[O:13])=[C:9]([F:11])[CH:10]=1

Komponenten

7

Edukt 4

HCID 95842-FluoroanilineHCID 10340Sodium Carbonate2×HCID 781249(6S)-1,4-Diazabicyclo(4.3.0)nonaneHCID 866439242-Chloro-5-(chlorosulfonyl)-4-fluorobenzoyl chloride

Produkt 1

HCID 468524404-chloro-2-fluoro-N-(2-fluorophenyl)-5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel4×

Versuchsvorschrift

To crude 2-chloro-5-(chlorosulfonyl)-4-fluorobenzoyl chloride (4 mmol) in anhydrous dichloromethane (100 mL) was added (S)-octahydropyrrolo[1,2-α]pyrazine (0.505 g, 4 mmol) in dichloromethane (10 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.933 g, 8.8 mmol) was added. The mixture was stirred at room temperature overnight. Then dichloromethane was removed by concentration in vacuo, and 2-fluoroaniline (4.44 g, 40 mmol) in dichloromethane (30 mL) was added. The mixture was stirred at room temperature for 4 days. At that time, sodium carbonate (0.42 g, 4 mmol) and methanol (20 mL) were added, the mixture was stirred for 30 minutes, then filtered, and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate, then methanol/ethyl acetate=1:15) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.20-1.38 (m, 1H), 1.60-2.20 (m, 7H), 2.80-3.40 (m, 4H), 4.40-4.60 (m, 1H), 7.20 (m, 4H), 7.60 (m, 1H), 7.88 (m, 1H), 10.60 (br s, 1H); MS (ESI) m/z 456 (M+H)+.

Aufarbeitung

  1. additionwas added
  2. stirringThe mixture was stirred at room temperature for 4 days
  3. stirringthe mixture was stirred for 30 minutes
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-8d9873eb007145089934dccd4a19d0d7
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08404719B2

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