反应详情

1.46 g (3.84 mmol) of the compound from Example 30A are introduced into 50 ml of ethyl acetate and, after addition of 777 mg (4.79 mmol) of 1,1′-carbonyldiimidazole, stirred at room temperature overnight. A TLC check (silica gel; mobile phase: ethyl acetate) shows complete conversion. The volatile components are removed in a rotary evaporator, and the residue is taken up in 20 ml of DMF. Then 10.74 ml of ammonia (28% by weight solution in water, 76.8 mmol) are added, and the reaction mixture is heated at 100° C. for 30 min. The solvent is distilled out under reduced pressure, and the residue is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). The residue after concentration of the product fractions is dissolved in 40 ml of dichloromethane/methanol (1:1 v/v) and mixed with 100 ml of ethyl acetate. The solvent is concentrated to a volume of about 20 ml, whereupon the product crystallizes. The precipitate is filtered off and washed with a little diethyl ether. Drying at 40° C. in a vacuum drying oven results in 1.40 g (96% of theory) of the title compound.

1. customThe volatile components are removed in a rotary evaporator
2. temperaturethe reaction mixture is heated at 100° C. for 30 min
3. distillationThe solvent is distilled out under reduced pressure
4. customthe residue is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5)
5. dissolutionThe residue after concentration of the product fractions is dissolved in 40 ml of dichloromethane/methanol (1:1 v/v)
6. additionmixed with 100 ml of ethyl acetate
7. concentrationThe solvent is concentrated to a volume of about 20 ml, whereupon the product
8. customcrystallizes
9. filtrationThe precipitate is filtered off
10. washwashed with a little diethyl ether
11. customDrying at 40° C. in a vacuum
12. customdrying oven