反应详情

N-(3-Chloro-4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-amine from Example 12A (3.00 g, 8.96 mmol) and (diethoxyphosphoryl)acetic acid (2.46 g, 12.5 mmol) were dissolved in DMF (60 mL). DIPEA (3.47 g, 26.9 mmol) and TBTU (4.32 g, 13.4 mmol) were added, and the reaction was stirred overnight at rt. Subsequently, the mixture was concentrated in vacuo, and the residue was dissolved in ethyl acetate. The solution was extracted with 1 M aqueous sodium hydroxide solution, dried over sodium sulfate, and the solvent was removed in vacuo. The residue was triturated with tert-butyl methyl ether. The precipitate was collected by suction filtration to yield 4.31 g (94%) of the title compound as white crystals.

1. concentrationSubsequently, the mixture was concentrated in vacuo
2. dissolutionthe residue was dissolved in ethyl acetate
3. extractionThe solution was extracted with 1 M aqueous sodium hydroxide solution
4. dry with materialdried over sodium sulfate
5. customthe solvent was removed in vacuo
6. customThe residue was triturated with tert-butyl methyl ether
7. filtrationThe precipitate was collected by suction filtration