Chloroform → 6-CHLOROPYRIDAZINE-3-CARBOXYLIC Acid (2-CYCLOBUTYLETHYL)AMIDE

Temperature

60 °C

To a 100-mL round bottom flask, 6-oxo-1,6-dihydropyridazine-3-carboxylic acid monohydrate (0.64 g, 3.6 mmol), chloroform (14 mL), dimethylformamide (0.1 mL) and thionyl chloride (1.2 mL) were added. The reaction mixture was stirred at 60° C. for 16 h. The reaction mixture was evaporated in vacuo to dryness. The solid residue was dissolved in dichloromethane (13 mL) and added dropwise to the mixture of cyclobutylethylamine (0.47 g, 4.74 mmol) and triethylamine (0.8 mL) in dichloromethane (25 mL) at ambient temperature. After stirred for 1 h, the reaction mixture was diluted with dichloromethane (100 mL) and washed sequentially with 10% aqueous HCl solution, saturated NaHCO3 and water. The organic layer was dried over Na2SO4 and evaporated in vacuum. Purification by column chromatography (silica gel, hexane/EtOAc (2:1)) afforded the product as a white powder (0.572 g, 59%). 1H NMR (300 MHz, CDCl3) δ 8.25, 7.97, 7.65, 3.42, 2.36, 2.08, 1.91-1.59.

1. customThe reaction mixture was evaporated in vacuo to dryness
2. dissolutionThe solid residue was dissolved in dichloromethane (13 mL)
3. stirringAfter stirred for 1 h
4. washwashed sequentially with 10% aqueous HCl solution, saturated NaHCO3 and water
5. dry with materialThe organic layer was dried over Na2SO4
6. customevaporated in vacuum
7. customPurification by column chromatography (silica gel, hexane/EtOAc (2:1))

ORD record

ord-3db81e2f47cb41f7a8be485307023e81

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07759348B2