Reacción #88788

Ecuación de reacción

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

3-(3-((tert-butyldimethylsilyl)oxy)propyl)-5-((4-chlorophenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Compound 20

3-(3-((tert-butyldimethylsilyl)oxy)propyl)-5-((4-chlorophenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Cs2CO3

2-(dimethylamino)acetic acid

dioxane

3-(trifluoromethyl)phenol

→

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

Rendimiento 62.3%

Disolventes

EA

water

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction was heated at 140° C. (MW) for 2 h
2. 2
   LavadoThe organic layer was washed with water (20 mL) and brine (20 mL)
3. 3
   Secadodried over Na2SO4
4. 4
   Concentraciónconcentrated to a residue which
5. 5
   Otrowas purified by chromatography
6. 6
   Lavadoeluted with PE/EA (10:1 to 1:1)

Procedimiento

To a mixture of 6-bromo-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4, 200 mg, 0.50 mmol), CuI (28.7 mg, 0.15 mmol), Cs2CO3 (327.2 mg, 1.00 mmol) and 2-(dimethylamino)acetic acid (10.4 mg, 0.10 mmol) in dioxane (3 mL) was added 3-(trifluoromethyl)phenol (162.8 mg, 1.00 mmol). The reaction was heated at 140° C. (MW) for 2 h, cooled to RT then diluted with EA (15 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-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (150 mg, 62.3% yield) as a white solid. LCMS: [MH+-THP] 396 and TR=1.941 min.

Fuente