Dimethyl Sulfoxide → N-(pyridazin-4-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

HRID 1666361Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1666361
Cl.N1C[CH2:6][C:5](=[C:8]2[CH:24]=[CH:23][CH:22]=[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][N:13]=3)[CH:9]2C)CC1.[N:26]1[CH:31]=[CH:30][C:29]([NH:32]C(=O)OC2C=CC=CC=2)=[CH:28][N:27]=1.[CH:42]([N:45]([CH:48]([CH3:50])C)[CH2:46][CH3:47])(C)C.CS(C)=[O:53]>>[N:26]1[CH:31]=[CH:30][C:29]([NH:32][C:42]([N:45]2[CH2:46][CH2:47][C:6](=[CH:5][C:8]3[CH:24]=[CH:23][CH:22]=[C:10]([O:11][C:12]4[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][N:13]=4)[CH:9]=3)[CH2:50][CH2:48]2)=[O:53])=[CH:28][N:27]=1

Komponenten

5

Edukt 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 14099147Phenyl pyridazin-4-ylcarbamateHCID 668763562-(3-Piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride

Produkt 1

HCID 24963362N-(pyridazin-4-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamideAusbeute 73 %

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of 2-(3-piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl pyridazin-4-ylcarbamate (0.215 g, 1.00 mmol, from Step 1) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and heated to 60° C. After 3 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was crystallized in a 1:1 mix of hexanes and ethyl ether to afford the title compound (335 mg, 73%) as white crystals. MS (APCI 10V) AP+ 456.16; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (t, J=5.46 Hz, 2H) 2.44 (t, J=5.46 Hz, 2H+DMSO) 3.49 (t, J=5.46 Hz, 2H) 3.56 (t, J=5.46 Hz, 2H) 6.39 (s, 1H) 7.03-7.04 (m, 2H) 7.12 (d, J=7.81 Hz, 1H) 7.21 (d, J=8.79 Hz, 1H) 7.39 (t, J=8.77 Hz, 1H) 7.74 (dd, J=5.86 Hz, 2.73 Hz, 1H) 8.20 (dd, J=8.60 Hz, 2.15 Hz, 1H) 8.54 (s, 1H) 8.58 (s, 1H) 8.85 (d, J=5.86 Hz, 1H) 9.20 (s, 1H) 9.25 (d, J=2.93 Hz, 1H).

Aufarbeitung

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted again with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was crystallized in a 1:1
  9. additionmix of hexanes and ethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-27a3ebdef4e0475e8590dedf7514d2d1
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044052B2

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