Cesium carbonate → 1-(7-Acetyl-5-chloroquinolin-8-yl)pyrrolidine-3-carbonitrile

HRID 1192600Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1192600
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.[NH:24]1[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:18]([C:8]1[C:7]([N:24]2[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]2)=[C:16]2[C:11]([CH:12]=[CH:13][CH:14]=[N:15]2)=[C:10]([Cl:17])[CH:9]=1)(=[O:20])[CH3:19]

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 42614784Pyrrolidine-3-carbonitrile hydrochlorideHCID 58368658HCID 58368658, Verbindung

Produkt 1

HCID 583686301-(7-Acetyl-5-chloroquinolin-8-yl)pyrrolidine-3-carbonitrileAusbeute 16 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.12 g, 0.34 mmol, from Example 47, Step 2), pyrrolidine-3-carbonitrile hydrochloride (0.054 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.31 g, 0.95 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4 and evaporated to dryness. The resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane) to give the desired product (16 mg, 16%). LCMS calculated for C16H15ClN3O (M+H)+: m/z=300.1; Found: 300.0.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-aaaf1407e22e4f7fb92131cc7fd2c91b
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680108B2

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