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

HRID 242013Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 242013
[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].CS(O[CH2:24][C:25]1[CH:26]=[N:27][C:28]([Br:31])=[CH:29][CH:30]=1)(=O)=O.[H-].[Na+].[Cl-].[NH4+]>O>[Br:31][C:28]1[N:27]=[CH:26][C:25]([CH2:24][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:30][CH:29]=1

Komponenten

6

Edukt 4

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 59281142(6-Bromopyridin-3-yl)methyl methanesulfonate2×HCID 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-79f15d50d9c249caba55f246422906cb
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653079B2

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