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

HRID 449977Notes

Reaction equation

HRID 449977 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-999afe4ebc134cd4a5fdf9d26f5afce4
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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