反応 #88454

反応方程式

3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(hydroxy(phenyl)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

3-(trifluoromethoxy)phenylboronic acid

K3PO4

→

3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxyl(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

収率 44.0%

溶媒

dioxane

water

反応条件

後処理

1. 1
   その他The reaction was degassed with nitrogen (3×)
2. 2
   温度heated at 120° C. (MW) for 2 h
3. 3
   workup.ADDITIONdiluted with EA (20 mL) and water (8 mL)
4. 4
   ろ過filtered through Celite
5. 5
   濃縮The filtrate was concentrated to a residue which
6. 6
   その他was purified by Prep TLC
7. 7
   洗浄eluted with PE/EA (2:1)

実験手順

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(hydroxy(phenyl)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (400 mg, 0.817 mmol), 3-(trifluoromethoxy)phenylboronic acid (336.9 mg, 1.635 mmol), aq. 2M K3PO4 (2 ml, 4.085 mmol) in dioxane (10 mL) and water (2 mL) was added Pd(dppf)Cl2 (21 mg, 0.0288 mmol). The reaction was degassed with nitrogen (3×), heated at 120° C. (MW) for 2 h, cooled to RT, diluted with EA (20 mL) and water (8 mL) and filtered through Celite. The filtrate was concentrated to a residue which was purified by Prep TLC eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxyl(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (220 mg, 44% yield) as colorless oil. LCMS: MH+ 616 and TR=2.334 min.

出典