反应详情

The title compound was prepared following the method of Example 20 using {2-amino-3-nitro-6-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyridin-4-yl}-benzyl-carbamic acid ethyl ester (174 mg) and Raney nickel (5 mg) in acetic acid (3 ml). This gave initially the SEM protected imidazole compound. Hydrogen chloride in dioxane (4 M, 1 ml) was then added drop-wise and the solution left to stir at room temperature for 24 hours. The reaction mixture was then transferred to a microwave vial (Biotage, 2-5 ml) and heated under microwave irradiation for 10 minutes at 110° C. (Biotage, Initiator 8). The reaction mixture was evaporated then re-dissolved in methanol and the solution loaded onto a cation-exchange cartridge (Bakerbond, sulphonic acid bonded-phase, 1 g). The cartridge was washed with methanol (2×5 ml) to remove impurities and then the product released by eluting with ammonia in methanol (2 M, 5 ml). The desired fractions were combined and evaporated to a brown solid. This was triturated with isopropanol and the solid collected by filtration then washed with more isopropanol, providing the title compound (28 mg) as a pale brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 5.02 (s, 2 H) 5.58 (s, 2 H) 6.91 (s, 1 H) 7.06 (s, 1 H) 7.11 (s, 1 H) 7.25-7.36 (m, 5 H) 10.53 (s, 1 H) 11.99 (s, 1 H). LCMS Rt=1.52 m/z 307 [MH]+hm

1. customThe title compound was prepared
2. customThis gave initially the SEM
3. waitthe solution left
4. customThe reaction mixture was evaporated
5. dissolutionthen re-dissolved in methanol
6. washThe cartridge was washed with methanol (2×5 ml)
7. customto remove impurities
8. washby eluting with ammonia in methanol (2 M, 5 ml)
9. customevaporated to a brown solid
10. customThis was triturated with isopropanol
11. filtrationthe solid collected by filtration
12. washthen washed with more isopropanol