Toluene → (3aR,6aR)-1-{4-[4-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-phenyl]-piperazin-1-yl}-ethanone

HRID 12962

Reaktionsgleichung

Reaktionsgleichung von HRID 12962
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C@@H:10]3[CH2:13][N:14]([CH3:16])[CH2:15][C@H:9]23)=[CH:4][CH:3]=1.[C:17]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)(=[O:19])[CH3:18].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:16][N:14]1[CH2:13][C@@H:10]2[C@@H:9]([N:8]([C:5]3[CH:6]=[CH:7][C:2]([N:23]4[CH2:24][CH2:25][N:20]([C:17](=[O:19])[CH3:18])[CH2:21][CH2:22]4)=[CH:3][CH:4]=3)[CH2:12][CH2:11]2)[CH2:15]1

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 837951-AcetylpiperazineHCID 23676156Sodium t-butoxideHCID 44221503(3aR,6aR)-1-(4-Bromophenyl)-5-methyloctahydropyrrolo[3,4-b]pyrrole

Produkt 1

HCID 68499336(3aR,6aR)-1-{4-[4-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-phenyl]-piperazin-1-yl}-ethanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

The product of Example 7C (500 mg, 1.78 mmole), 1-acetylpiperazine (274 mg, 2.13 mmole), tris(dibenzylideneacetone)dipalladium (32.6 mg, 0.036 mmole), (r)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthylwere (44.3 mg, 0.071 mmole), sodium tert-butoxide (256 mg, 2.67 mmole) and 5 ml of toluene were mixed under N2 in a Emrys process vials. The vial was sealed, then heated in the microwave for 20 minutes at 150° C., using the Emrys Creator microwave reactor. The mixture was diluted with water and extracted with dichloromethane (4×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography (eluting with a mixture of 10% methanol and 1% ammonium hydroxide in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 6.87-6.91 (m, 2H) 6.53-6.60 (m, 2H) 4.05-4.07 (m, 1H) 3.73-3.79 (m, 2H) 3.57-3.63 (m, 2H) 3.46-3.54 (m, 1H) 3.12-3.20 (m, 1H) 2.96-3.03 (m, 4H) 2.56-2.71(m, 5H) 2.34 (s, 3H) 2.14-2.18 (m, 1H) 2.13 (s, 3H) 1.87-1.97 (m, 1H). MS: (M+H)+=329.

Aufarbeitung

  1. customThe vial was sealed
  2. extractionextracted with dichloromethane (4×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by column chromatography (
  8. washeluting with a mixture of 10% methanol and 1% ammonium hydroxide in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-f45e3224072b4607a152ae29c51b9d83
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728031B2

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