反应详情

Phosgene (20% in toluene, 1 mL, 2.0 mmol, 2.4 equiv) is added to a solution of 2,6-dichloro-3,5-dimethoxyaniline (221 mg, 1.0 mmol, 1.2 equiv) in dioxane (2.5 mL), under an argon atmosphere. The mixture is heated to reflux, stirred for 1 h, allowed to cool to RT, and concentrated in vacuo. The resulting isocyanate is added to a solution of N-methyl-N′-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-pyrimidine-4,6-diamine (Step 2.1) (259 mg, 0.83 mmol) in toluene (5 mL), at reflux and under an argon atmosphere. The reaction mixture is stirred at reflux for 3 h, allowed to cool to RT, and diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted with DCM. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 95:5) affords the title compound as a yellow solid: ESI-MS: 560.0/562.0 [MH]+; tR=3.26 min (purity: 99%, system 1); TLC: Rf=0.37 (DCM/MeOH+1% NH3aq, 9:1).

1. temperatureThe mixture is heated
2. temperatureto reflux
3. concentrationconcentrated in vacuo
4. temperatureat reflux and under an argon atmosphere
5. stirringThe reaction mixture is stirred
6. temperatureat reflux for 3 h
7. temperatureto cool to RT
8. customThe aqueous layer is separated
9. extractionextracted with DCM
10. washThe organic phase is washed with brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customPurification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 95:5)