Reaktion #88788

Reaktionsgleichung

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

Ausbeute 62.3%

Lösungsmittel

EA

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction was heated at 140° C. (MW) for 2 h
2. 2
   WaschenThe organic layer was washed with water (20 mL) and brine (20 mL)
3. 3
   Trocknendried over Na2SO4
4. 4
   Einengenconcentrated to a residue which
5. 5
   Sonstigewas purified by chromatography
6. 6
   Wascheneluted with PE/EA (10:1 to 1:1)

Vorschrift

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.

Quelle