Sodium hydride → Ethyl 1-[(6-bromopyridin-3-yl)methyl]-8-chloro-4-oxo-1,4-dihydrocinnoline-3-carboxylate

HRID 449977Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 449977
[CH2:1]([O:3][C:4](=[O:18])[C:5](=[N:16][NH2:17])[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=1F)=[O:7])[CH3:2].[H-].[Na+].CS(O[CH2:26][C:27]1[CH:28]=[N:29][C:30]([Br:33])=[CH:31][CH:32]=1)(=O)=O.[Cl-].[NH4+]>O>[Br:33][C:30]1[N:29]=[CH:28][C:27]([CH2:26][N:17]2[C:9]3[C:8](=[CH:13][CH:12]=[CH:11][C:10]=3[Cl:14])[C:6](=[O:7])[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:18])=[N:16]2)=[CH:32][CH:31]=1

Komponenten

6

Edukt 4

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 59281142(6-Bromopyridin-3-yl)methyl methanesulfonateHCID 178472855ethyl 3-(3-chloro-2-fluorophenyl)-2-hydrazinylidene-3-oxopropanoate

Produkt 1

HCID 86659998Ethyl 1-[(6-bromopyridin-3-yl)methyl]-8-chloro-4-oxo-1,4-dihydrocinnoline-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Ethyl-3-(3-chloro-2-fluorophenyl)-2-hydrazinylidene-3-oxopropanoate [(Example 60, Step 1), 1.9 g, 7.0 mmol] and (6-bromopyridin-3-yl) methyl methanesulfonate (2.4 g, 9.1 mmol, 1.3 equiv) were dissolved in degassed N,N′-dimethyl formamide, cooled to 0° C. and treated with sodium hydride (0.45 g, 11 mmol, 1.6 equiv). After stirring at 0° C. for 3 hours, additional (6-bromopyridin-3-yl)methyl methanesulfonate (0.55 g, 2.1 mmol, 0.3 equiv) and sodium hydride (84 mg, 2.1 mmol, 0.3 equiv) were added and stirred for an additional 5 hours. The mixture was treated with ammonium chloride (10 mL, aqueous saturated), poured into water (50 mL) and extracted three times with ethyl acetate. The combined organic extracts were washed once with water and brine, dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 96:4; chloroform:methanol), providing the titled compound.

Aufarbeitung

  1. stirringstirred for an additional 5 hours
  2. extractionextracted three times with ethyl acetate
  3. washThe combined organic extracts were washed once with water and brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel gradient chromatography (100:0 to 96:4; chloroform:methanol)

Quellen und Nachweise

ORD-Eintrag
ord-999afe4ebc134cd4a5fdf9d26f5afce4
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486946B2

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