反应详情

2-[2-(3-Chloro-phenyl)-ethoxy]-acetamidine hydrochloride (240 mg, 0.964 mmol; described in example 6.2) was dissolved in MeOH (2 ml) and NaOMe (30% solution in MeOH, 179 μl, 0.964 mmol) was added dropwise at 0° C. The suspension was stirred at ambient temperature for 15 min and then evaporated. To the remaining residue were added a solution of crude 3-chloro-pyridazine-4-carboxylic acid ethyl ester (180 mg) in DMF (3 ml) and subsequently K2CO3 (267 mg, 1.929 mmol) and the mixture was heated to 100° C. for 18 h. Then water was added, the pH was adjusted to 3 by addition of 0.1 N HCl and the mixture was extracted three times with CH2Cl2 and one time with ethyl acetate. The combined organic extracts were washed three times with diluted HCl (pH 3), dried (Na2SO4) and evaporated. The remaining residue was triturated with Et2O and the brown solid was filtered off and further purified by column chromatography (silica gel, CH2Cl2/MeOH 95:5) to give the title compound (11 mg, 0.035 mmol; 3.6%) as brown solid. MS: m/e=317.1 [M+H+].

1. customevaporated
2. temperaturethe mixture was heated to 100° C. for 18 h
3. extractionthe mixture was extracted three times with CH2Cl2 and one time with ethyl acetate
4. washThe combined organic extracts were washed three times with diluted HCl (pH 3)
5. dry with materialdried (Na2SO4)
6. customevaporated
7. customThe remaining residue was triturated with Et2O
8. filtrationthe brown solid was filtered off
9. customfurther purified by column chromatography (silica gel, CH2Cl2/MeOH 95:5)