反应详情

温度

0 °C

5.7 g of chlorosulfonylisocyanate are added dropwise at 0°-5° C. to a solution of 7 g of 2-amino-4-difluoromethoxy-6-methylpyrimidine in 100 ml of absolute tetrahydrofuran. The yellowish solution is stirred for 10 minutes at 0° C., then 5.6 ml of pyrrole are added and the reaction mixture is stirred for 17 hours at 20°-25° C. The solvent is evaporated off and the residue is taken up in a mixture of 25 ml of methanol, 50 ml of water and 3.2 g of sodium hydroxide. The solution is shaken vigorously for 10 minutes, washed with two 50 ml portions of methylene chloride and acidified with glacial acetic acid. The acid aqueous solution is then extracted with ethyl acetate. The organic extracts are dried over magnesium sulfate and concentrated to give a 1:1 mixture of two isomers in 20% yield. This mixture of isomers is chromatographed over silica gel with a 4:1 mixture of petroleum ether/ethyl acetate, affording N-(2-pyrrolylsulfonyl)-N'-4-difluoromethoxy-6-methylpyrimidin-2-yl)urea with a melting point of 189° C. (compound 4.1) and N-(3-pyrrolylsulfonyl)-N'-(4-difluoromethoxy-6-methylpyrimidin-2-yl)urea with a melting point of 173°-174° C. (compound 4.8).

1. stirringthe reaction mixture is stirred for 17 hours at 20°-25° C
2. customThe solvent is evaporated off
3. additionthe residue is taken up in a mixture of 25 ml of methanol, 50 ml of water and 3.2 g of sodium hydroxide
4. stirringThe solution is shaken vigorously for 10 minutes
5. washwashed with two 50 ml portions of methylene chloride
6. extractionThe acid aqueous solution is then extracted with ethyl acetate
7. dry with materialThe organic extracts are dried over magnesium sulfate
8. concentrationconcentrated
9. customto give
10. additiona 1:1 mixture of two isomers in 20% yield
11. additionThis mixture of isomers
12. customis chromatographed over silica gel with a 4:1 mixture of petroleum ether/ethyl acetate