Toluene → 3-Methoxy-5-[4-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-3',5'-bis(trifluoromethyl)biphenyl-2-yl]pyridine

HRID 383775

Reaktionsgleichung

Reaktionsgleichung von HRID 383775
Br[C:2]1[CH:7]=[C:6]([C:8]([N:10]2[CH2:14][CH2:13][CH:12]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[CH2:11]2)=[O:9])[CH:5]=[CH:4][C:3]=1[C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1.[CH3:35][O:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:42]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>CCO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:35][O:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41]([C:2]2[CH:7]=[C:6]([C:8]([N:10]3[CH2:14][CH2:13][CH:12]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)[CH2:11]3)=[O:9])[CH:5]=[CH:4][C:3]=2[C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[CH:42]=1

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 38661613-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 866577533-(1-{[2-Bromo-3',5'-bis(trifluoromethyl)biphenyl-4-yl]carbonyl}pyrrolidin-3-yl)pyridine

Produkt 1

HCID 866577523-Methoxy-5-[4-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-3',5'-bis(trifluoromethyl)biphenyl-2-yl]pyridine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.7 mg, 0.019 mmol) was added to a solution of 3b (51.0 mg, 0.094 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (24.3 mg, 0.103 mmol) and sodium carbonate (94.0 μL, of a 2.0 M aqueous solution, 0.188 mmol) in EtOH:toluene (1.25 mL of an 80:20 mixture, respectively) at rt. The resulting solution was heated to 125° C. in a sealed microwave vial for 12 min. After cooling to rt, the reaction mixture was filtered through a short column of Celite®, eluting with EtOAc. The filtrate was washed with water and brine, dried (sodium sulfate) and concentrated in vacuo. The crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier), followed by lyophilization of the purified fractions afforded the title compound 3c. m/z (ES) 572 (MH)+.

Aufarbeitung

  1. customat rt
  2. temperatureAfter cooling to rt
  3. filtrationthe reaction mixture was filtered through a short column of Celite®
  4. washeluting with EtOAc
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier)

Quellen und Nachweise

ORD-Eintrag
ord-375568f3d46d434fbe85ed83ce9dcafc
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367679B2

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