反应详情

温度

80 °C

tert-Butyl 4-chloro-5,8-dihydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine-7(6H)-carboxylate from Example 11A (407.5 g, 1.251 mol) was dissolved in 2-propanol (5.7 L). 3,4-Dichloroaniline (213.8 g, 1.313 mol) and a 4 M solution of gaseous hydrogen chloride in dioxane (17.4 mL, 63 mmol) were added. The mixture was heated to 80° C. for 3 days. The thick suspension was then diluted with additional 2-propanol (1 L), and further 4 M hydrogen chloride in dioxane (695 mL, 2.5 mol) was added. The mixture was again heated to 80° C. for 3 h. The solvent was then removed in vacuo, and the residue was treated with 1 M aqueous sodium hydroxide solution (12 L). The precipitate was collected by suction filtration and washed with water. The product was dried for 2 days at 50° C., then triturated with tert-butyl methyl ether and collected by suction filtration to yield 413 g (92%) of the title compound.

1. additionwas added
2. temperatureThe mixture was again heated to 80° C. for 3 h
3. customThe solvent was then removed in vacuo
4. additionthe residue was treated with 1 M aqueous sodium hydroxide solution (12 L)
5. filtrationThe precipitate was collected by suction filtration
6. washwashed with water
7. customThe product was dried for 2 days at 50° C.
8. customtriturated with tert-butyl methyl ether
9. filtrationcollected by suction filtration