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

HRID 1666336

Reaktionsgleichung

Reaktionsgleichung von HRID 1666336
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.[C:26]1([N:32]=[C:33]=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(C(C)C)CC)(C)C.C([O-])([O-])=O.[K+].[K+]>ClCCl>[C:26]1([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:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Komponenten

6

Edukt 4

HCID 7672Phenyl isocyanateHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

Produkt 1

HCID 24968340N-phenyl-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamideAusbeute 22,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenylisocyanate (0.143 g, 1.2 mmol) in dichloromethane (20 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and stirred at RT for 18 h. The reaction mixture was stirred with 10% K2CO3 for 1 h and then partitioned after diluting with additional dichloromethane (200 mL). The combined organic layer was washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (1% of the 1N NH3 in MeOH, in dichloromethane) to afford the title compound (100 mg, 22%) as a white solid after trituration with diethyl ether. MS (APCI 10V) AP+ 454.28; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (t, J=5.46 Hz, 2H) 2.46 (t, J=5.46 Hz, 2H) 3.29 (s, 3H) 3.46 (t, J=5.46 Hz, 2H) 3.54 (t, J=5.46 Hz, 2H) 6.37 (s, 1H) 6.89 (t, J=8.60 Hz, 1H) 7.03 (m, 2H) 7.12 (d, J=7.60 Hz, 1H) 7.19-7.22 (m, 3H) 7.38 (d, J=7.8 Hz, 1H) 7.41 (d, J=8.77 Hz, 2H) 8.20 (dd, J=8.8 Hz, 2.8 Hz, 1H) 8.50 (s, 1H) 8.55 (s, 1H).

Aufarbeitung

  1. custompartitioned
  2. additionafter diluting with additional dichloromethane (200 mL)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (1% of the 1N NH3 in MeOH

Quellen und Nachweise

ORD-Eintrag
ord-95543d6edbd545fb8181e8bdcddeb51f
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044052B2

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