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

HRID 1666365Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1666365
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.[Cl:26][C:27]1[N:32]=[C:31]([NH:33]C(=O)OC2C=CC=CC=2)[CH:30]=[N:29][CH:28]=1.[CH:43]([N:46]([CH:49]([CH3:51])C)[CH2:47][CH3:48])(C)C.CS(C)=[O:54]>>[Cl:26][C:27]1[N:32]=[C:31]([NH:33][C:43]([N:46]2[CH2:47][CH2:48][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)[CH2:51][CH2:49]2)=[O:54])[CH:30]=[N:29][CH:28]=1

Komponenten

5

Edukt 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 668763562-(3-Piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochlorideHCID 86623895Phenyl 6-chloropyrazin-2-ylcarbamate

Produkt 1

HCID 24963705N-(6-chloropyrazin-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamideAusbeute 36 %

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of 2-(3-piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.370 g, 1.00 mmol) (from Example 1, Step 5) and phenyl 6-chloropyrazin-2-ylcarbamate (0.262 g, 1.00 mmol, from Step 1) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.170 g, 1.6 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 purified by silica gel chromatography (5% of 1N NH3 in MeOH, in dichloromethane) to afford the title compound (175 mg, 36%) as white crystals after trituration in diethyl ether. MS (APCI 10V) AP+ 490.13; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.32 (s, 3H) 2.34 (t, J=5.46 Hz, 2H) 2.45 (t, J=5.46 Hz, 2H) 3.46 (t, J=5.46 Hz, 2H) 3.54 (t, J=5.46 Hz, 2H) 6.39 (s, 1H) 7.02-7.04 (m, 2H) 7.12 (d, J=7.60 Hz, 1H) 7.21 (d, J=8.20, Hz, 1H) 7.39 (t, J=8.01 Hz, 1H) 8.20 (dd, J=5.28 Hz, 2.74 Hz, 2H) 8.25 (s, 1H) 9.0 (s, 1H) 9.90 (s, 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 (5% of 1N NH3 in MeOH, in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-117df1302f634f298b0cb16221916eab
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044052B2

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