反应详情

A modified procedure of the procedure described by Leonard, N. J., et al., J. Am. Chem. Sec. 69:2459 (1947), was followed. Cyanogen bromide (136.6 g, 1.3M, 260 mL of a 5M solution in CH3CN from) was added to a solution of MeOH (250 mL) in H2O (1500 mL). 4,5-Dichloro-1,2-phenylenediamine (available commercially from Aldrich Chemical Company) (222.4 g, 1.26M) was then added in five portions, as the initial reaction is exothermic. The reaction mixture was stirred without heating for 80 hr. then treated with activated charcoal (5 g). The 80 hr time period was for convenience alone, since the reaction is probably complete within 24 hr. After stirring for two hrs, the reaction mixture was filtered through Celite. The filter cake was washed with MeOH (250 mL) and H2O (750 mL) and the filter cake was discarded. The filtrate was diluted with H2O (1.5 L), adjusted to pH 10 with conc. NH4OH (1750 mL) and then allowed to stand overnight at 5° C. The precipitate (yellow leaflets) was collected by filtration, washed with H2O and then dried under reduced pressure at 50° C. for 60 hr. Crude yield: 265 g. This product was purified by recrystallization from CH3CN to yield: 205.6 g (80.7%) of 4. MP: 264°-266° C. TLC: Rf =0.22 (CHCl3 --MeOH), 10:1; SiO2). See Horner, J. K. et al., J. Med. Chem. 11:946-949 (1968), lit. MP: 260°-262° C. As an alternative, the crude material is dissolved in absolute ethanol, treated with activated charcoal, and the solution diluted with an equal volume of H2O and stored at 5° C. for 18-24 hr.

1. customas the initial reaction
2. temperaturewithout heating for 80 hr
3. customThe 80 hr time period
4. stirringAfter stirring for two hrs
5. filtrationthe reaction mixture was filtered through Celite
6. washThe filter cake was washed with MeOH (250 mL) and H2O (750 mL)
7. additionThe filtrate was diluted with H2O (1.5 L)
8. waitto stand overnight at 5° C
9. filtrationThe precipitate (yellow leaflets) was collected by filtration
10. washwashed with H2O
11. customdried under reduced pressure at 50° C. for 60 hr
12. customThis product was purified by recrystallization from CH3CN to yield: 205.6 g (80.7%) of 4
13. dissolutionAs an alternative, the crude material is dissolved in absolute ethanol
14. additiontreated with activated charcoal
15. additionthe solution diluted with an equal volume of H2O
16. waitstored at 5° C. for 18-24 hr