Sodium hydride → Ethyl-8-chloro-1-(4-iodobenzyl)-4-oxo-1,4-dihydrocinnoline-3-carboxylate

HRID 242011Notes

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].[I:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Br)=[CH:22][CH:21]=1.[H-].[Na+].[Cl-].[NH4+]>CN(C)C=O.O>[CH2:1]([O:3][C:4]([C:5]1[C:6](=[O:7])[C:8]2[C:9](=[C:10]([Cl:14])[CH:11]=[CH:12][CH:13]=2)[N:17]([CH2:24][C:23]2[CH:26]=[CH:27][C:20]([I:19])=[CH:21][CH:22]=2)[N:16]=1)=[O:18])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

Ethyl-3-(3-chloro-2-fluorophenyl)-2-hydrazinylidene-3-oxopropanoate [(Example 60, Step 2) 1.61 g, 5.90 mmol] and 4-iodobenzyl bromide (2.28 g, 7.68 mmol, 1.3 equiv) were dissolved in degassed N,N-dimethylformamide (20 mL), cooled to 0° C. and treated with sodium hydride (378 mg, 9.45 mmol, 1.6 equiv). After stirring for 2 hours at 0° C., the mixture was treated with ammonium chloride (25 mL, 25% aqueous), warmed to ambient temperature, diluted with water (100 mL) and extracted with ethyl acetate (3×50 mL). 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 20:80; hexanes:ethyl acetate), providing the titled compound.

Workup

temperaturewarmed to ambient temperature
extractionextracted with ethyl acetate (3×50 mL)
washThe combined organic extracts were washed once with water and brine
dry with materialdried with sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel gradient chromatography (100:0 to 20:80; hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-21620672821c4769a198bba298476cf8
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653079B2

Reaction notes

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