反应详情

温度

-10 °C

Nitric acid (90%), 125 mL, was stirred and cooled to -10° C., and 125 mL of 98% sulfuric acid was added dropwise. Upon completion of addition, the reaction mixture temperature was brought to 0° C., and 19.7 grams (0.10 mole) of 2,4-diamino-5-chloroquinazoline (Compound 2, prepared in a manner analogous to that of Step E of Example 1) was added. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it was stirred for about 18 hours. The reaction mixture was then poured into 1500 mL of ice. The resultant mixture was made basic with 700 mL of aqueous 30% ammonia, keeping the temperature below 30° C. The mixture was cooled in an ice-bath, and the resultant solid was collected by filtration. The solid was stirred with 1000 mL of tetrahydrofuran and 500 mL of water. The mixture was filtered to remove a solid. The filtrate was diluted with 500 mL of ethyl acetate and then was concentrated under reduced pressure to a solid residue. The two solids were combined, washed with ethyl acetate, and dried, yielding 22.2 grams of 2,4-diamino-5-chloro-6-nitroquinazoline. The NMR spectrum was consistent with the proposed structure.

1. additionUpon completion of addition
2. customwas brought to 0° C.
3. additionwas added
4. additionUpon completion of addition
5. temperatureto warm to ambient temperature where it
6. customthe temperature below 30° C
7. temperatureThe mixture was cooled in an ice-bath
8. filtrationthe resultant solid was collected by filtration
9. stirringThe solid was stirred with 1000 mL of tetrahydrofuran and 500 mL of water
10. filtrationThe mixture was filtered
11. customto remove a solid
12. additionThe filtrate was diluted with 500 mL of ethyl acetate
13. concentrationwas concentrated under reduced pressure to a solid residue
14. washwashed with ethyl acetate
15. customdried