Hydrochloric Acid → (1-{3-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Temperature

50 °C

To a solution of 3-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (1.0 g, 2.4 mmol) in methanol (20 mL) was added 4.0 M solution of HCl in dioxane (4.0 mL, excess). The mixture was stirred for 3 hours at 50° C. and concentrated under reduced pressure. The residue was treated with ether to remove excess HCl. The obtained white solid was dissolved in DMF (20 mL). To the solution was added 2-methoxycarbonylamino-3-methyl-butyric acid (0.46 g, 2.6 mmol), HATU (1.0 g, 2.6 mmol) and N,N-diisopropylethylamine (2.5 mL, 14.4 mmol). The mixture was stirred at ambient for 2 hours, and then the volatile component was removed in vacuo. The residue was dissolved in ethyl acetate (200 mL), washed with 1 N NaOH solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product as a white solid (1.0 g, 89%). m/z 475.1, 477.1 (M+H)+.

1. concentrationconcentrated under reduced pressure
2. additionThe residue was treated with ether
3. customto remove excess HCl
4. dissolutionThe obtained white solid was dissolved in DMF (20 mL)
5. stirringThe mixture was stirred at ambient for 2 hours
6. customthe volatile component was removed in vacuo
7. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
8. washwashed with 1 N NaOH solution, water and brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe obtained residue was purified by flash chromatography

ORD record

ord-6fb28d2144154c629f50bf00966fd924

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822430B2