Chloride → Methyl 6-(4-hydroxypiperidin-1-yl)pyridazine-3-carboxylate

A solution of 6-chloropyridazine-3-carboxylic acid (0.50 g, 3.2 mmol) in 11 mL of SOCl2 was heated at 75° C. for 2 h and was then concentrated and redissolved in 5 mL of MeOH. To the solution was added a 25% solution of sodium methoxide (0.75 mL, 3.5 mmol, 1.1 eq) in MeOH. The reaction mixture was stirred at room temperature for 20 h and was then quenched with H2O and extracted with dichloromethane. Silica gel flash chromatography (EtOAc/MeOH 90:10) of the residue afford a 2:1 mixture of the 6-chloropyridazine-3-carboxylic acid and 6-methoxypyridazine-3-carboxylic acid (0.160 g). To a solution of the mixture of ester and chloride in 1.9 mL of p-dioxane was added 4-hydroxy piperidine (0.094 g, 93 mmol) followed by diisopropylethylamine (0.49 mL, 2.8 mmol). The mixture was heated at 100° C. for 20 h then concentrated. Purification with silica gel flash chromatography afforded methyl 6-(4-hydroxypiperidin-1-yl)pyridazine-3-carboxylate (0.15 g, 63 mmol).

1. concentrationwas then concentrated
2. dissolutionredissolved in 5 mL of MeOH
3. customwas then quenched with H2O
4. extractionextracted with dichloromethane
5. customSilica gel flash chromatography (EtOAc/MeOH 90:10) of the residue afford
6. temperatureThe mixture was heated at 100° C. for 20 h
7. concentrationthen concentrated
8. customPurification with silica gel flash chromatography

ORD record

ord-aee8372e6551426ba88f83a27e814aea

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169261B2