Reaktion #88740

Reaktionsgleichung

3-chlorophenol

3-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Cs2CO3

2-(dimethylamino)acetic acid

→

5-(4-chlorobenzyl)-6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Ausbeute 12.3%

Lösungsmittel

EA

water

dioxane

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 Prep HPLC

Vorschrift

To a mixture of 3-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (80 mg, 0.17 mmol), CuI (4.2 mg, 0.022 mmol), Cs2CO3 (167.6 mg, 0.51 mmol) and 2-(dimethylamino)acetic acid (8.8 mg, 0.085 mmol) in dioxane (2 mL) was added 3-chlorophenol (55.1 mg, 0.43 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 Prep HPLC to give 5-(4-chlorobenzyl)-6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (10.2 mg, 12% yield) as a white solid. 1H NMR (CDCl3) δ: 8.35 (s, 1H), 7.23 (d, J=8.2 Hz, 1H), 7.17 (s, 4H), 7.09 (d, J=8.0 Hz, 1H), 6.84-6.73 (m, 2H), 4.71 (s, 2H), 4.24 (t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.55 (s, 2H), 3.02 (s, 1H), 2.00-1.86 (m, 2H). LCMS: MH+ 486 and TR=3.332 min.

Quelle