反应详情

To a solution of N4-ethyl-pyridine-3,4-diamine (Justus Liebigs Ann. Chem. (1935) 518, 274, 287) (125 mg, 0.9 mmol) in dichloroethane (10 mL) is added a solution of AlMe3 in toluene (2M, 1.37 mL) dropwise under nitrogen. After addition, the mixture is stirred at room temperature for one hour and (2-pyrimidin-2-yl-imidazol-1-yl)-acetic acid methyl ester (100 mg, 0.45 mmol) is added in one portion. The reaction mixture is heated with stirring at 80° C. for 2 days. After cooled, the mixture is quenched with 5 mL of water, 2 drops of 5 N NaOH and extracted with CH2Cl2 (10 mL×5). The combined organic extracts are dried over Na2SO4, and concentrated. The residue is dissolved in 10 mL of acetic acid and the resulting mixture is heated at 100° C. overnight. After removal of acetic acid under vacuum, the residue is basified with saturated NaHCO3 solution and extracted with CH2Cl2 (10 mL×5). The combined organic extracts are dried over Na2SO4, and concentrated. The residue is purified on a silica gel column with 10:1 CH2Cl2/MeOH as eluent to yield the title compound (40 mg). 1H NMR (CDCl3) δ: 9.09 (s, 1H), 8.85 (d, 2H), 8.46 (d, 1H), 7.26-7.30 (m, 3H), 7.16 (1H), 6.39 (s, 2H), 4.25 (q, 2H), 1.15 (t, 3H).

1. additionAfter addition
2. temperatureThe reaction mixture is heated
3. stirringwith stirring at 80° C. for 2 days
4. temperatureAfter cooled
5. customthe mixture is quenched with 5 mL of water, 2 drops of 5 N NaOH
6. extractionextracted with CH2Cl2 (10 mL×5)
7. dry with materialThe combined organic extracts are dried over Na2SO4
8. concentrationconcentrated
9. dissolutionThe residue is dissolved in 10 mL of acetic acid
10. temperaturethe resulting mixture is heated at 100° C. overnight
11. customAfter removal of acetic acid under vacuum
12. extractionextracted with CH2Cl2 (10 mL×5)
13. dry with materialThe combined organic extracts are dried over Na2SO4
14. concentrationconcentrated
15. customThe residue is purified on a silica gel column with 10:1 CH2Cl2/MeOH as eluent