反应详情

To a solution of N-(3-Amino-4-methyl-phenyl)-3-trifluoromethyl-benzamide (preparation 3, 62 mg, 0.21 mmol, 1.25 eq.) in dioxane is added 20% phosgene solution in toluene (110 μl, 0.21 mmol, 1.25 eq.) under argon. The reaction mixture is stirred for further 22 h at room temperature under argon. Then, the solvent is evaporated and the residue is taken up in dry toluene (2 ml). After the addition of N-Methyl-N′-[4-(4-methyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamine (50 mg, 0.168 mmol, 1.0 eq.) the suspension is refluxed for 24 h under argon. After cooling ether (2 ml) is added and the mixture is stirred for 30 min. The precipitated product is filtered off, washed (1× toluene/ether 1:1, 1× ether) and vacuum dried at 60° C. overnight to afford the title compound as colorless crystals: M.p. 189.5-191° C., HPLC: tR=6.02 min (purity: >99%, gradient A), ESI-MS: 619.6 [MH]+.

1. customThen, the solvent is evaporated
2. temperatureis refluxed for 24 h under argon
3. additionis added
4. stirringthe mixture is stirred for 30 min
5. filtrationThe precipitated product is filtered off
6. washwashed (1× toluene/ether 1:1, 1× ether) and vacuum
7. customdried at 60° C. overnight