4-(Trifluoromethyl)aniline → 4-chloro-3-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide

HRID 400509Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 400509
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH2:15]1[NH:20][CH2:19][CH2:18][N:17]2[CH2:21][CH2:22][CH2:23][C@H:16]12.C(=O)([O-])[O-].[Na+].[Na+].[F:30][C:31]([F:40])([F:39])[C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1>ClCCl.CO>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([NH:36][C:35]2[CH:37]=[CH:38][C:32]([C:31]([F:30])([F:39])[F:40])=[CH:33][CH:34]=2)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([N:20]1[CH2:19][CH2:18][N:17]2[CH2:21][CH2:22][CH2:23][C@@H:16]2[CH2:15]1)=[O:5]

Komponenten

7

Edukt 4

HCID 99644-(Trifluoromethyl)anilineHCID 10340Sodium Carbonate2×HCID 7004239(8aR)-Octahydropyrrolo(1,2-a)pyrazineHCID 545501992-Chloro-5-(chlorosulfonyl)benzoyl chloride

Produkt 1

HCID 468516554-chloro-3-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

To crude 2-chloro-5-(chlorosulfonyl)benzoyl chloride (2 mmol) in anhydrous dichloromethane (50 mL) was added (R)-octahydropyrrolo[1,2-a]pyrazine (0.252 g, 2 mmol) in dichloromethane (4 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.46 g, 4.4 mmol) was added. The mixture was stirred at room temperature overnight. Then dichloromethane was removed by concentration, and 4-(trifluoromethyl)aniline (3.22 g, 20 mmol) was added. The mixture was stirred at 70° C. overnight. Then sodium carbonate (0.21 g, 2 mmol) and methanol (5 mL) were added at room temperature. 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=1:10) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.30 (m, 1H), 1.55 (m, 1H), 1.70-2.00 (m, 4H), 2.60 (m, 2H), 2.80-3.50 (m, 4H), 4.40-4.60 (m, 1H), 7.30 (m, 2H), 7.62 (m, 2H), 7.82 (m, 3H), 11.00 (br s, 1H); MS (ESI) m/z 488 (M+H)+.

Aufarbeitung

  1. additionwas added
  2. stirringThe mixture was stirred at 70° C. overnight
  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-24a5ad4037d141079fc06e5d0e9bcf33
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741899B2

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