Binap, (A+-)- → (3aR,6aR)-6-{4-[4-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-phenyl]-piperazin-1-yl}-nicotinonitrile

HRID 12961

Reaktionsgleichung

Reaktionsgleichung von HRID 12961
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.[N:17]1([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][N:24]=2)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.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:20]4[CH2:21][CH2:22][N:17]([C:23]5[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][N:24]=5)[CH2:18][CH2:19]4)=[CH:3][CH:4]=3)[CH2:12][CH2:11]2)[CH2:15]1

Komponenten

8

Edukt 4

HCID 634876Binap, (A+-)-HCID 27371846-(Piperazin-1-yl)pyridine-3-carbonitrileHCID 23676156Sodium t-butoxideHCID 44221503(3aR,6aR)-1-(4-Bromophenyl)-5-methyloctahydropyrrolo[3,4-b]pyrrole

Produkt 1

HCID 24743685(3aR,6aR)-6-{4-[4-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-phenyl]-piperazin-1-yl}-nicotinonitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

The product of Example 7C (281.2 mg, 1.0 mmole), the product of Example 48A (226 mg, 1.2 mmole), tris(dibenzylideneacetone)dipalladium (18.3 mg, 0.02 mmole), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (25.0 mg, 0.04 mmole) and sodium tert-butoxide (145 mg, 1.5 mmole) were dissolved in 5 ml of toluene and heated at 70° C. under N2 for 24 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane (5×). The combined organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure and purified by chromatography (eluting with a mixture of 5% methanol in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.43 (d, J=1.70 Hz, 1H) 7.62 (dd, J=8.98, 2.20 Hz, 1H) 6.92 (d, J=8.81 Hz, 2H) 6.64 (d, J=9.15 Hz, 1H) 6.56 (d, J=9.15 Hz, 2H) 4.01-4.15 (m, 1H) 3.79-3.88 (m, 4H) 3.45-3.55 (m, 1H) 3.14-3.23 (m, 1H) 3.08-3.14 (m, 4H) 2.97-3.04 (m, 1H) 2.55-2.75 (m, 4H) 2.36 (s, 3H) 2.09-2.22 (m, 1H) 1.92 (m, 1H); MS (M+H)+=389.

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (5×)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. custompurified by chromatography (
  7. washeluting with a mixture of 5% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-abefc20c9383425cb4c7e8a560d784a4
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728031B2

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