1-Naphthol → 4-methyl-2-[4-(naphthalen-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

Temperature

25 °C

A solution of 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (0.30 g, 0.57 mmol) in acetonitrile (12 mL, 0.048M) was treated with cesium carbonate (0.37 g, 1.14 mmol) and naphthalen-1-ol (0.10 g, 0.69 mmol). The resulting reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was then concentrated in vacuo and partitioned between water (100 mL) and ethyl acetate (100 mL). The organics were washed with a saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (AnaLogix 40 g, 25-75% ethyl acetate/hexanes) afforded 4-methyl-2-[4-(naphthalen-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (208.7 mg, 68%) as a light orange solid as a mixture of diastereomers.

1. customThe resulting reaction mixture
2. concentrationThe reaction mixture was then concentrated in vacuo
3. custompartitioned between water (100 mL) and ethyl acetate (100 mL)
4. washThe organics were washed with a saturated aqueous sodium chloride solution (50 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. washrinsed
8. concentrationconcentrated in vacuo

ORD record

ord-ba4c88b4e973468b91d41c5815babeb6

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258134B2