反应详情

Under an argon stream, N,N-dimethylacetamide (351 ml, 5.0 v/w) was added to methyl 4-(N-(4-(4-(4-cyclohexylbenzylamino)phenyl)-2-thiazolyl)-N-methylaminomethyl)benzoate (70.3 g, 0.134 mol) obtained in Example 1(5) and potassium carbonate (73.9 g, 0.535 mol) was carefully added with stirring. After stirring the mixture at room temperature for 20 min., dimethyl sulfate (50.6 ml, 0.535 mol) was added. After stirring at 50° C. for 1 hr., potassium carbonate (18.4 g, 0.134 mol) and dimethyl sulfate (12.7 ml, 0.134 mol) were added and the mixture was stirred at 60° C. for 2 hr. After cooling to room temperature, n-hexane (422 ml, 6.0 v/w) was added, and the mixture was stirred for 1 hr. After ice-cooling, distilled water (562 ml, 8.0 v/w) was added. After stirring at room temperature for 1 hr., the resulting crystals were collected by filtration and washed with methanol (352 ml, 5.0 v/w) in a slurry form. Tetrahydrofuran (180 ml) was added to the obtained orange solid and insoluble materials were filtered off. The filtrate was concentrated to give the title compound (42.1 g, yield 58.3%) as a pale-yellow solid.

1. additionwas carefully added
2. stirringAfter stirring the mixture at room temperature for 20 min.
3. stirringAfter stirring at 50° C. for 1 hr
4. stirringthe mixture was stirred at 60° C. for 2 hr
5. stirringthe mixture was stirred for 1 hr
6. temperatureAfter ice-cooling
7. distillationdistilled water (562 ml, 8.0 v/w)
8. additionwas added
9. stirringAfter stirring at room temperature for 1 hr
10. filtration, the resulting crystals were collected by filtration
11. washwashed with methanol (352 ml, 5.0 v/w) in a slurry form
12. additionTetrahydrofuran (180 ml) was added to the obtained orange solid and insoluble materials
13. filtrationwere filtered off
14. concentrationThe filtrate was concentrated