반응 #88433

반응 방정식

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

수율 20.1%

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) and 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-((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.

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