反応 #88433

反応方程式

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

Compound 49

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

4-chlorophenylboronic acid

NaHCO3

K3PO4

→

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

収率 20.1%

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 1.5 h
3. 3
   workup.ADDITIONthen diluted with EA (10 mL) and water (2 mL)
4. 4
   ろ過The reaction was filtered
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-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (See Compound 49, step 4, 130 mg, 0.248 mmol), 4-chlorophenylboronic acid (77.37 mg, 0.496 mmol), NaHCO3 (62.5 mg, 0.744 mmol) and aq. 2M K3PO4 (0.62 ml, 1.24 mmol) in dioxane (1 mL) and water (0.2 mL) was added Pd(dppf)Cl2 (7 mg, 0.0096 mmol). The reaction was degassed with nitrogen (3×) and heated at 120° C. (MW) for 1.5 h, cooled to RT then diluted with EA (10 mL) and water (2 mL). The reaction was filtered and 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)-6-(4-chlorophenyl)-5-((4-chlorophenyl)(hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 20% yield) as colorless oil, LCMS: MH+ 600 and TR=2.924 min.

出典