反应详情

To a solution of tert-butyl{2-[2′-(3-methoxypropyl)-3-methylbiphenyl-4-yl]-3-pyridin-3-ylpropyl}carbamate from step 3 (1 eq.) in CH2Cl2 (0.1M) was added ZnBr2 (10 eq.). The mixture was sonicated for 30 min, filtered on a plug of silica gel. The latter was washed with CH2Cl2/MeOH (NH3 2M) 10% and the combined fractions were concentrated. The residue was purified by reverse phase HPLC (C18 column; gradient 40 to 90% of CH3CN/H2O/TFA 0.1%). Fractions containing the desired material were combined, concentrated, neutralized with NaOH (1N) and extracted with CH2Cl2. The combined extract was dried over Na2SO4, filtered and concentrated. The residue was dissolved in CH2Cl2, acidified with HCl (4N in dioxane; 4 eq.) and the resulting suspension was triturated with addition of Et2O to afford after filtration the title compounds as a light yellow solid. 1H NMR (500 MHz, DMSO-d6): δ 8.71 (d, 1H), 8.67 (s, 1H), 8.27 (br s, 3H), 7.98 (d, 1H), 7.56 (brt, 1H), 7.47 (d, 1H), 7.31 (s, 1H), 7.30 (s, 1H), 7.28-7.22 (m, 1H), 7.18 (d, 1H), 7.12 (d, 1H), 7.02 (s, 1H), 3.74-3.64 (m, 1H), 3.45 (brdd, 1H), 3.21-3.17 (m, 4H), 3.13 (s, 3H), 3.04 (dd, 1H), 2.61-2.50 (m, 2H), 2.08 (s, 3H), 1.65-1.55 (m, 2H).

1. customThe mixture was sonicated for 30 min
2. filtrationfiltered on a plug of silica gel
3. washThe latter was washed with CH2Cl2/MeOH (NH3 2M) 10%
4. concentrationthe combined fractions were concentrated
5. customThe residue was purified by reverse phase HPLC (C18 column; gradient 40 to 90% of CH3CN/H2O/TFA 0.1%)
6. additionFractions containing the desired material
7. concentrationconcentrated
8. extractionextracted with CH2Cl2
9. extractionThe combined extract
10. dry with materialwas dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. dissolutionThe residue was dissolved in CH2Cl2
14. customthe resulting suspension was triturated with addition of Et2O
15. customto afford
16. filtrationafter filtration the title compounds as a light yellow solid