Diisopropylethylamine → N-(6-methoxypyridin-3-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

HRID 1666335

Reaktionsgleichung

Reaktionsgleichung von HRID 1666335
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.[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31]([NH:34][C:35]([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:36])=[CH:30][CH:29]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 20185962Phenyl 6-methoxypyridin-3-ylcarbamateHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

Produkt 1

HCID 24967994N-(6-methoxypyridin-3-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamideAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

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 phenyl 6-methoxypyridin-3-ylcarbamate (0.244 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 50° 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 purified by silica gel chromatography (10% of the 1N NH3 in MeOH, in dichloromethane) to afford the title compound (280 mg, 58%) as white crystals after trituration in diethyl ether. MS (APCI 10V) AP+ 485.30; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (t, J=5.46 Hz, 2H) 2.46 (t, J=5.46 Hz, 2H) 3.46 (t, J=5.46 Hz, 2H) 3.54 (t, J=5.46 Hz, 2H) 3.76 (s, 3H) 6.38 (s, 1H) 6.69 (d, J=8.77 Hz, 1H) 7.03 (m, 2H) 7.12 (d, J=7.80 Hz, 1H) 7.21 (d, J=8.60 Hz, 1H) 7.4 (dd, J=8.5 Hz, 1 Hz, 1H) 7.73 (dd, J=8.9 Hz, 2.7 Hz, 1H) 8.14 (d, J=2.5 Hz, 1H) 8.20 (dd, J=8.77 Hz, 2.5 Hz, 1H) 8.49 (s, 1H) 8.55 (d, J=2.5 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 purified by silica gel chromatography (10% of the 1N NH3 in MeOH

Quellen und Nachweise

ORD-Eintrag
ord-e17c6628834d45ef8c154c153e1a472b
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044052B2

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