Potassium Carbonate → 2-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[8a-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-2(1h)-yl]-3-pyridinyl}-n,2-dimethylpropanamide

HRID 2074925Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2074925
[CH2:1]1[NH:6][CH2:5][CH2:4][N:3]2[CH2:7][CH2:8][CH2:9][C:2]12[CH2:10][OH:11].[F:12][C:13]([F:47])([F:46])[C:14]1[CH:15]=[C:16]([C:24]([CH3:45])([CH3:44])[C:25]([N:27]([C:29]2[CH:30]=[N:31][C:32](Cl)=[CH:33][C:34]=2[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[CH3:42])[CH3:28])=[O:26])[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[F:23][C:20]([F:21])([F:22])[C:18]1[CH:17]=[C:16]([C:24]([CH3:45])([CH3:44])[C:25]([N:27]([C:29]2[CH:30]=[N:31][C:32]([N:6]3[CH2:5][CH2:4][N:3]4[CH2:7][CH2:8][CH2:9][C:2]4([CH2:10][OH:11])[CH2:1]3)=[CH:33][C:34]=2[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[CH3:42])[CH3:28])=[O:26])[CH:15]=[C:14]([C:13]([F:47])([F:12])[F:46])[CH:19]=1

Komponenten

6

Edukt 3

HCID 11430Potassium Carbonate2×HCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 45122045(Octahydropyrrolo[1,2-a]pyrazin-8a-yl)methanol

Produkt 1

HCID 160640382-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[8a-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-2(1h)-yl]-3-pyridinyl}-n,2-dimethylpropanamideAusbeute 10,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a solution of hexahydropyrrolo[1,2-a]pyrazin-8a(6H)-ylmethanol (D67, 35 mg) in methyl sulfoxide (1.5 mL), 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (60 mg) and potassium carbonate (63 mg) were added. The resulting mixture was heated at 150° C. for 24 hours. The mixture was allowed to cool down to r.t and further D67 (17 mg) and potassium carbonate (15 mg) were added. The resulting mixture was heated at 150° C. for further 8 hours and then it was allowed to cool to r.t. and diluted with water (2 mL). The aqueous phase was extracted with ethyl acetate (3×2.5 mL). The combined organic extracts were dried and concentrated in vacuo to a residue which was purified twice by flash chromatography (first purification: EtOAc/Cycl from 80/20 to 100:0 then DCM/MeOH 95:5. Second purification: DCM/MeOH 98:2) to give the desired compound (7.7 mg) as yellow foam.

Aufarbeitung

  1. temperatureto cool down
  2. temperatureThe resulting mixture was heated at 150° C. for further 8 hours
  3. temperatureto cool to r.t.
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×2.5 mL)
  5. customThe combined organic extracts were dried
  6. concentrationconcentrated in vacuo to a residue which
  7. customwas purified twice by flash chromatography (
  8. customfirst purification
  9. customSecond purification

Quellen und Nachweise

ORD-Eintrag
ord-1ef9d2b7fb164b6bba20dd80dede7d92
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919491B2

Notizen zur Reaktion

Wird geladen…