Sodium hydride → Ethyl 1-[(6-chloropyridin-3-yl)methyl]-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

HRID 2067104Notes

Reaction equation

[O:1]=[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6][NH:5][C:4]2[N:13]=[CH:14][CH:15]=[CH:16][C:3]1=2.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24]Cl)=[CH:20][N:19]=1.[H-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:17][C:18]1[N:19]=[CH:20][C:21]([CH2:24][N:5]2[C:4]3[N:13]=[CH:14][CH:15]=[CH:16][C:3]=3[C:2](=[O:1])[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6]2)=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Ethyl 4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate (1.00 g, 4.56 mmol) and 2-chloro-5-(chloromethyl)pyridine (813 mg, 5.02 mmol, 1.1 equiv) were combined in degassed N,N-dimethylformamide and cooled to 0° C. Sodium hydride (219 mg, 5.47 mmol, 1.2 equiv) was added portionwise over 5 minutes and the mixture was stirred for an additional 1 hour at 0° C. The mixture was warmed to ambient temperature, stirred for 1 hour and poured into sodium bicarbonate (150 mL, aqueous saturated). The aqueous layer was extracted with ethyl acetate (2×150 mL) and the combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound as a white solid.

Workup

temperatureThe mixture was warmed to ambient temperature
stirringstirred for 1 hour
extractionThe aqueous layer was extracted with ethyl acetate (2×150 mL)
dry with materialthe combined organic extracts were dried with sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-5f77da195d5f46c1a5b698d2e4d4a833
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293744B2

Reaction notes

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