反应详情

To sulfolane (20 mL) was added phosphoryl chloride (7.40 g, 48.3 mmol). Triethylamine (4.88 g, 48.3 mmol) was added dropwise, and the mixture was stirred for 30 min at rt. Subsequently, tert-butyl 4-oxo-3,4,5,6,7,9-hexahydro-8H-pyrimido[5′,4′:4,5]thieno[2,3-c]azepine-8-carboxylate from Example 78A (5.17 g, 16.1 mmol) was added, and the reaction mixture was heated for 2 h to 65° C. The mixture was then cooled to rt, and triethylamine (7.0 mL) was added. It was diluted with toluene and cooled to 0° C. Half-saturated aqueous sodium chloride solution was added, and the mixture was stirred for 20 min. The organic layer was separated, washed with water and dried over sodium sulfate, and the solvent was removed in vacuo. The residue was triturated with tert-butyl methyl ether, and the precipitate was collected by suction filtration to yield 4.40 g (80%) of the title compound.

1. temperaturethe reaction mixture was heated for 2 h to 65° C
2. temperatureThe mixture was then cooled to rt
3. temperaturecooled to 0° C
4. stirringthe mixture was stirred for 20 min
5. customThe organic layer was separated
6. washwashed with water
7. dry with materialdried over sodium sulfate
8. customthe solvent was removed in vacuo
9. customThe residue was triturated with tert-butyl methyl ether
10. filtrationthe precipitate was collected by suction filtration