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

HRID 2067115Notes

Reaction equation

HRID 2067115 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.[I:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1.[H-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[I:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][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:20][CH:19]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 9542584-Iodobenzyl bromideHCID 66745620Ethyl 4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate2×

Product 1

HCID 66744748Ethyl 1-[(4-iodophenyl)methyl]-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

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 [(Example 5, Step 1), 500 mg, 2.28 mmol] and 4-iodobenzylbromide (745 mg, 2.51 mmol, 1.1 equiv) were dissolved in degassed N,N-dimethylformamide (5 mL) and cooled to 0° C. The mixture was treated with sodium hydride (109 mg, 2.74 mmol, 1.2 equiv) portionwise over 5 minutes. After stirring for 2 hours at 0° C., the mixture was warmed to ambient temperature and stirred for an additional 2 hours. The mixture was treated with sodium bicarbonate (10 mL, aqueous saturated), poured into water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried with sodium sulfate, filtered, concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound.

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for an additional 2 hours
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-811211e9424c4dd78ee74159e528db23
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

Loading…