反应详情

To a solution of 2,6-dichloro-3,5-dimethoxyaniline (preparation 2, 74 mg, 0.34 mmol, 1.25 eq.) in dioxane is added 20% phosgene solution in toluene (191 μl, 0.36 mmol, 1.35 eq.) under argon. The reaction mixture is stirred for further 6 h at room temperature under argon. Then, the solvent is evaporated and the colorless crystalline residue is taken up in dry toluene (2.5 ml). After the addition of N-methyl-N′-[4-(4-methyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamine (see example 1, 80 mg, 0.27 mmol, 1.0 eq.) the suspension is stirred at 70° C. for 36 h under argon. After cooling the precipitate is filtered off, washed with toluene, methanol/ether 1:1, and ether to give a beige powder. The crude product is purified by flash chromatography (1% MeOH in DCM to 16% MeOH in DCM within 30 min). The fractions containing the product are pooled, evaporated, and triturated with ether. The precipitate is filtered off, washed (1× cold methanol/ether 1:1, 1× ether), and vacuum dried at 45° C. over night to afford the title compound as colorless powder: m.p. 221° C. (dec.), ESI-MS: 546.1/548.0/550.0 [MH]+.

1. customThen, the solvent is evaporated
2. stirringis stirred at 70° C. for 36 h under argon
3. temperatureAfter cooling the precipitate
4. filtrationis filtered off
5. washwashed with toluene, methanol/ether 1:1, and ether
6. customto give a beige powder
7. customThe crude product is purified by flash chromatography (1% MeOH in DCM to 16% MeOH in DCM within 30 min)
8. additionThe fractions containing the product
9. customevaporated
10. customtriturated with ether
11. filtrationThe precipitate is filtered off
12. washwashed (1× cold methanol/ether 1:1, 1× ether), and vacuum
13. customdried at 45° C. over night