Water → HCID 178439895, compound

[step 1] To a mixture of methyl 2-amino-5-bromobenzoate (2.3 g, 10.0 mmol) and propionic anhydride (14 mL) was added dropwise fuming nitric acid (2.1 mL, 50.0 mmol) under ice-cooling. After stirring at 70° C. for 15 min, water and ethyl acetate were added to the mixture, and the mixture was extracted. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=70/30) to give methyl 3-amino-5-bromo-2-butylamidobenzoate (1.23 g, 36%). [step 2] Methyl 3-amino-5-bromo-2-butylamidobenzoate (1.22 g, 3.53 mmol) obtained in step 1 was dissolved in methanol (20 mL) and the mixture was stirred in the presence of 10% palladium carbon (240 mg) under a hydrogen atmosphere at room temperature for 7 hr. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in acetic acid (1 mL), and the mixture was stirred at 100° C. for 1 hr. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol=90/10) to give methyl 2-propylbenzimidazole-4-carboxylate (0.299 g, 39%). [step 3] Methyl 2-propylbenzimidazole-4-carboxylate (0.295 g, 1.35 mmol) obtained in step 2 was dissolved in THF (10 mL), 3 mol/L methylmagnesium chloride THF solution (4.5 mL, 13 mmol) was added under ice-cooling, and the mixture was stirred at room temperature for 1 hr. To the mixture were added water and ethyl acetate, and the mixture was extracted. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=90/10) to give the title compound (0.201 g, 68%).

1. temperaturecooling
2. extractionthe mixture was extracted
3. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel column chromatography (chloroform/methanol=90/10)

ORD record

ord-e538cfed956d4cd7b076e23a26a0e24a

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486980B2