反应详情

To a solution of 2,6-dichloro-3,5-dimethoxy-aniline (124 mg, 0.56 mmol; Preparation 2) in 2 ml of dioxane under a nitrogene atmosphere, phosgene (0.52 ml 20% in toluene, 0.98 mmol) is added. The mixture is stirred for 70 min at 100° C., cooled to RT and concentrated in vacuo, yielding 2,6-dichloro-3,5-dimethoxyphenylisocyanate. The resulting solid is added portion-wise to a boiling solution of N-methyl-N′-[4-(4-methyl-piperazin-1-yl)-phenyl]-[1,3,5]triazine-2,4-diamine (140 mg, 0.47 mmol) in 8 ml of toluene during 20 min. After 3 h, another 2 eq of 2,6-dichloro-3,5-dimethoxyphenylisocyanate are added and stirring is continued for totally 5 h. Then the reaction mixture is diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted twice with DCM. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; DCM/MeOH/NH3aq, 97:3:0.2) gives the title compound: ESI-MS: 547/549 [MH]+; tR=3.5 min (purity: 100%, gradient J); TLC: Rf=0.40 (DCM/MeOH+1% NH3aq, 95:5).

1. waitis continued for totally 5 h
2. customThe aqueous layer is separated
3. extractionextracted twice with DCM
4. washThe organic phases are washed with water and brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated