反应详情

Phosgene (20% in toluene, 1.62 mL, 3.0 mmol, 2.0 equiv) is added to a solution of 5-methoxy-3-trifluoromethylaniline (344 mg, 1.8 mmol, 1.2 equiv) in dioxane (6 mL) under a nitrogen atmosphere. The mixture is heated to reflux, stirred for 80 min, allowed to cool to RT, and concentrated in vacuo. During 45 min, a concentrated solution of the resulting oily 5-methoxy-3-trifluoromethyl-phenylisocyanate in toluene is added portion-wise to a boiling solution of N-[4-(4-ethyl-piperazin-1-yl)-phenyl]-N′-methyl-pyrimidine-4,6-diamine (468 mg, 1.50 mmol; Step 242.1) in 18 ml of toluene under a nitrogen atmosphere. The reaction mixture is stirred at 110° C. for 4 h, allowed to cool to RT, and 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 brine, dried (Na2SO4), filtered and concentrated. Column chromatography (DCM/MeOH, 49:1→24:1) provides the title compound: API-MS: 530/532 [MH]+; TLC: Rf=0.4 (DCM/MeOH, 9:1); tR=4.3 min (purity: 100%, system 1).

1. temperatureThe mixture is heated
2. temperatureto reflux
3. concentrationconcentrated in vacuo
4. waitDuring 45 min
5. stirringThe reaction mixture is stirred at 110° C. for 4 h
6. temperatureto cool to RT
7. customThe aqueous layer is separated
8. extractionextracted twice with DCM
9. washThe organic phases are washed with brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated