Cesium carbonate → benzyl (1S,5S)-6-(5-cyano-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane-3-carboxylate

HRID 1642187

Reaktionsgleichung

Reaktionsgleichung von HRID 1642187
[C@@H:1]12[CH2:7][NH:6][C@@H:5]1[CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[CH2:2]2.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:25]1[CH:26]=[N:27][CH:28]=[C:29]([C:31]#[N:32])[CH:30]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.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].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:31]([C:29]1[CH:30]=[C:25]([N:6]2[CH2:7][C@@H:1]3[C@H:5]2[CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:2]3)[CH:26]=[N:27][CH:28]=1)#[N:32]

Komponenten

8

Edukt 3

HCID 10796Cesium carbonateHCID 7367935-BromonicotinonitrileHCID 23635906benzyl (1S,5S)-3,6-diazabicyclo[3.2.0]heptane-3-carboxylate

Produkt 1

HCID 23635910benzyl (1S,5S)-6-(5-cyano-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane-3-carboxylateAusbeute 64,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 634876Binap, (A+-)-KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

The product of Example 52D (830 mg, 3.58 mmol) in toluene (20 mL) was treated with Pd2(dba)3 (71.0 mg, 0.072 mmol), BINAP (134 mg, 0.214 mmol), Cs2CO3 (2.32 g, 7.16 mmol) and 3-bromo-5-cyanopyridine (0.98 g, 5.37 mmol). The mixture was heated at 100° C. under N2 for 10 hours and then allowed to cool to room temperature and diluted with ethyl acetate (100 mL). The brown solution was washed with water (2×10 mL) and concentrated under reduced pressure. The residue was purified by chromatography (SiO2, EtOAc:hexane, 50:50, Rf 0.3) to provide the title compound (770 mg, 64% yield). 1H NMR (MeOH-d4, 300 MHz) δ 3.2(dd, J=12.9, 4. Hz, 1H), 3.30-3.4 (m, 2H), 3.6 (dd, J=8.2, 3. Hz, 1H), 3.96-4.10 (m, 3H), 4.74 (dd, J=6.1, 4.0 Hz, 1H), 5.10 (m, 2H), 7.15 (dd, J=2.7, 1.7 Hz, 1H), 7.25 (m, 3H), 7.35 (m, 2H), 7.96 (d, J=2.7 Hz, 1H), 8.15 (d, J=1.7 Hz, 1H); MS (DCI/NH3) m/z 335 (M+H)+.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. washThe brown solution was washed with water (2×10 mL)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by chromatography (SiO2, EtOAc:hexane, 50:50, Rf 0.3)

Quellen und Nachweise

ORD-Eintrag
ord-eb4cc527aa66444ba1dd5a9754e18eea
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08119635B2

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