Cesium carbonate → 3-({4-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]benzyl}amino)benzonitrile

HRID 12968

Reaktionsgleichung

Reaktionsgleichung von HRID 12968
[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:15]=[CH:14][C:13]([CH2:16][NH2:17])=[CH:12][CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1.Br[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[C:22]#[N:23].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.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:19]4[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=4)[C:22]#[N:23])=[CH:12][CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 233813-BromobenzonitrileHCID 634876Binap, (A+-)-HCID 247437821-{4-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]phenyl}methanamine

Produkt 1

HCID 247437833-({4-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]benzyl}amino)benzonitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

The product of Example 69 (40 mg, 0.173 mmole), 3-bromobenzonitrile (47 mg, 0.258 mmole), tris(dibenzylideneacetone)dipalladium (16 mg, 0.017 mmole), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (21 mg, 0.034 mmole) and cesium carbonate (85 mg, 0.26 mmole) were dissolved in 1 ml of toluene and heated at 100° C. under N2 for 48 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane (3×). The combined organics were dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by chromatography (eluting with a mixture of 2% basic methanol in dichloromethane) to provide the title compound. 1H NMR (CDCl3) δ ppm 9.73 (s, 1H) 7.72 (d, J=8.82 Hz, 2H) 7.30-7.54 (m, 2H) 7.14-7.22 (m, 1H) 6.77-6.88 (m, 1H) 6.56 (t, J=8.65 Hz, 2H) 4.22-4.33 (m, 1H) 4.19 (s, 2H) 3.36-3.64 (m, 2H) 2.90-3.08 (m, 1H) 2.66-2.79 (m, 2H) 2.52-2.63 (m, 2H) 2.32 (s, 3H) 2.09-2.26 (m, 1H) 1.87-2.04 (m, 1H); MS (M+H)+=333.

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (3×)
  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 2% basic methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-34c7d2f4da1447a19c0d48f9e5a9e60d
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728031B2

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