Diisopropylethylamine → N-pyridin-3-yl-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide Phenyl pyridin-3-ylcarbamate

HRID 1666321

Reaktionsgleichung

Reaktionsgleichung von HRID 1666321
Cl.[NH:2]1[CH2:7][CH2:6][C:5](=[CH:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][CH:25]=2)[O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=2)[CH2:4][CH2:3]1.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][C:33](=[O:41])[O:34]C2C=CC=CC=2)[CH:27]=1.C(N(C(C)C)CC)(C)C>C(#N)C>[C:9]1([N:32]([C:28]2[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=2)[C:33](=[O:41])[OH:34])[CH:10]=[CH:11][CH:23]=[CH:24][CH:25]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][C:33]([N:2]2[CH2:7][CH2:6][C:5](=[CH:8][C:9]3[CH:25]=[CH:24][CH:23]=[C:11]([O:12][C:13]4[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][N:14]=4)[CH:10]=3)[CH2:4][CH2:3]2)=[O:34])[CH:27]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

Produkt 1

HCID 86623891N-pyridin-3-yl-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide Phenyl pyridin-3-ylcarbamateAusbeute 79,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

2-(3-Piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (800 mg, 2.16 mmol, from Step 5), phenyl pyridin-3-ylcarbamate (508 mg, 2.37 mmol) and diisopropylethylamine (0.75 mL, 4.52 mmol) were combined in acetonitrile (10 mL) and stirred at room temperature. After 16 hours, the reaction was concentrated forming a residue and the residue was partitioned between EtOAc and water. The organic layer was separated, washed with 5% NaOH (aq), dried over anhydrous sodium sulfate, filtered and concentrated. Treatment of the residue with hot isopropyl ether and purified from isopropyl ether/methanol provided the title compound as a white solid (574 mg). MS (APCI 10V) AP+ 455.3, 376.2, 335.2, AP− 453.2; 1H NMR (400 MHz, CD3OD) δ ppm 2.46 (td, J=5.86, 0.97 Hz, 2H) 2.58 (td, J=5.82, 1.16 Hz, 2H) 3.51-3.60 (m, 2H) 3.61-3.70 (m, 2H) 6.46 (s, 1H) 6.98-7.07 (m, 2H) 7.09-7.19 (m, 2H) 7.34 (ddd, J=8.41, 4.81, 0.65 Hz, 1H) 7.40 (td, J=7.69, 0.74 Hz, 1H) 7.91 (ddd, J=8.38, 2.58, 1.44 Hz, 1H) 8.08 (ddd, J=8.73, 2.61, 0.55 Hz, 1H) 8.16 (dd, J=4.84, 1.06 Hz, 1H) 8.43 (td, J=1.74, 0.91 Hz, 1H) 8.58 (d, J=1.88 Hz, 1H).

Aufarbeitung

  1. concentrationthe reaction was concentrated
  2. customforming a residue
  3. customthe residue was partitioned between EtOAc and water
  4. customThe organic layer was separated
  5. washwashed with 5% NaOH (aq)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customTreatment of the residue with hot isopropyl ether and purified from isopropyl ether/methanol

Quellen und Nachweise

ORD-Eintrag
ord-e61d7a4aa4cf4c678432658c950d2d75
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044052B2

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