Реакция #88708

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-(trifluoromethyl)pyridine

→

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

Выход 64.3%

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-(trifluoromethyl)pyridine (842.9 mg, 3.73 mmol). The reaction was heated at 135° C. for 5 hours, followed by heating at 100° C. for 18 h, cooled to RT and 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 1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (460 mg, 64.2% yield) as a yellow oil. LCMS MH+ 397 and TR=1.540 min.

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