반응 #88436

반응 방정식

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

4-chlorophenyl boronic acid

NaHCO3

K3PO4

→

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

수율 26.0%

용매

dioxane

water

반응 조건

후처리

1. 1
   기타The reaction was degassed with nitrogen (3×)
2. 2
   온도heated at 120° C. (MW) for 1.5 h
3. 3
   workup.ADDITIONthen diluted with EA (10 mL) water (2 mL)
4. 4
   여과The reaction was filtered
5. 5
   농축the filtrate was concentrated to a residue which
6. 6
   기타was purified by Prep TLC
7. 7
   세척eluted with PE/EA (2:1)

실험 절차

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (100 mg, 0.212 mmol), 4-chlorophenyl boronic acid (66 mg, 0.424 mmol), NaHCO3 (53 mg, 1.06 mmol), aq. 2M K3PO4 (0.53 ml, 1.06 mmol) in dioxane (1 mL) and water (0.2 mL) was added Pd(dppf)Cl2 (5 mg, 0.0068 mmol). The reaction was degassed with nitrogen (3×), heated at 120° C. (MW) for 1.5 h, cooled to RT then diluted with EA (10 mL) 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-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 26% yield) as a colorless oil. LCMS: MH+ 546 and TR=2.602 min.

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