1-(Methoxymethyl)benzoimidazole → (1-(methoxymethyl)-1H-benzo[d]imidazol-2-yl)(3-((3-nitropyridin-2-yl)amino)-cyclobutyl)methanone

Temperature

-78 °C

To a solution of 1-(methoxymethyl)-1H-benzo[d]imidazole (1.5 g, 9.04 mmol) in dry tetrahydrofuran (20 mL) at −78° C. was added butyllithium (2.5 M in hexane, 3.7 mL, 9.16 mmol). The solution was stirred at −78° C. for 30 min and a solution of N-methoxy-N-methyl-3-((3-nitropyridin-2-yl)amino)cyclobutanecarboxamide (1.92 g, 6.87 mmol) in dry tetrahydrofuran (20 mL) was added dropwise via cannula. The reaction mixture was stirred at −78° C. for 30 minutes and then warmed to room temperature and quenched with water. The reaction mixture was extracted with ethyl acetate (3×30 mL) and the organic phases were combined and washed with water (20 mL), then brine (20 mL). The organic was dried over magnesium sulfate and concentrated to get a residue, which was purified by flash column chromatography on silica gel (10% to 40% ethyl acetate in hexanes) to give (1-(methoxymethyl)-1H-benzo[d]imidazol-2-yl)(3-((3-nitropyridin-2-yl)amino)-cyclobutyl)methanone (1.17 g, 3.07 mmol, 80% yield) as solid.

1. stirringThe reaction mixture was stirred at −78° C. for 30 minutes
2. temperaturewarmed to room temperature
3. customquenched with water
4. extractionThe reaction mixture was extracted with ethyl acetate (3×30 mL)
5. washwashed with water (20 mL)
6. dry with materialThe organic was dried over magnesium sulfate
7. concentrationconcentrated
8. customto get a residue, which
9. customwas purified by flash column chromatography on silica gel (10% to 40% ethyl acetate in hexanes)

ORD record

ord-8e4caf15a4644ccc983951a35c04edbb

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174992B2