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

HRID 242013Notes

Reaction equation

HRID 242013 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].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

Participants

6

Reactant 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

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-79f15d50d9c249caba55f246422906cb
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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