反应详情

To a slurry of 4-difluoromethoxy-6-methoxypyrimidin-2-amine (0.56 g, 2.92 mmol) in dry dichloromethane (5 mL) was added a solution of methyl 4-ethoxy-2-(isocyanatosulfonyl)benzoate (crude, ca. 5.6 mL) in dichloromethane (5 mL). The reaction mixture was heated at reflux for 3 hours, during which time the solid dissolved. On stirring at room temperature for 12 hours a new solid formed. The crude reaction mixture was chromatographed directly on a column of silica gel using as eluant 40:1, 20:1, and finally 10:1 dichloromethane-ether, all containing 2 mL/L acetic acid. The appropriate fractions were diluted with toluene and rotary evaporated to give a solid. The solid was slurried in hexanes, collected, washed with butyl chloride, 1:1 butyl chloride-hexanes, hexanes and air dried. The product was a white crystalline solid melting at 195°-196° C. PMR (CDCl3, 200 MHz): δ 12.02 (bs, 1H); 7.91 (d, 1H); 7.78 (d, 1H); 7.52 (t, 1H); 7.34 (bs, 1H); 7.09 (dd, 1H); 5.97 (s, 1H); 4.17 (q, 2H); 4.12 (s, 3H); 3.87 (s, 3H); 1.46 (t, 3H). IR (Nujol): 1722 (vs, C=O) cm-1.

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 3 hours, during which time the solid
3. dissolutiondissolved
4. customformed
5. customThe crude reaction mixture
6. customwas chromatographed directly on a column of silica gel using as eluant 40:1, 20:1, and finally 10:1 dichloromethane-ether
7. additionThe appropriate fractions were diluted with toluene
8. customrotary evaporated
9. customto give a solid
10. customcollected
11. washwashed with butyl chloride, 1:1 butyl chloride-hexanes, hexanes and air
12. customdried