Реакция #88704

Уравнение реакции

6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Compound 36

6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Cs2CO3

2-(dimethylamino)acetic acid

3-bromo-5-chloropyridine

→

6-((5-chloropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Выход 78.8%

Растворители

dioxane

EA

water

Условия реакции

Обработка

1. 1
   Температураby heating at 100° C. for 18 h
2. 2
   Температураcooled to RT
3. 3
   ПромывкаThe organic layer was washed with water (20 mL) and brine (20 mL)
4. 4
   Сушкаdried over Na2SO4
5. 5
   Концентрированиеconcentrated to a residue which
6. 6
   Другоеwas purified by chromatography
7. 7
   Промывкаeluted with PE/EA (10:1 to 1:1)

Методика

To a mixture of 6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 2, 500 mg, 1.49 mmol), CuI (85.2 mg, 0.45 mmol), Cs2CO3 (971.6 mg, 2.98 mmol) and 2-(dimethylamino)acetic acid (76.87 mg, 0.75 mmol) in dioxane (20 mL) was added 3-bromo-5-chloropyridine (717.3 mg, 3.73 mmol). The reaction was heated at 135° C. for 5 h followed by heating at 100° C. for 18 h, cooled to RT then diluted with EA (25 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 6-((5-chloropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (525 mg, 78.8% yield) as a yellow oil. LCMS [MH+-THP] 363 and TR=1.403 min.

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