Phosgene → HCID 23630277, compound

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Reaction Steps

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).

Provenance & Evidence