تفاعل #88441

معادلة التفاعل

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

2-isopropyl phenylboronic acid

NaHCO3

K3PO4

→

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

المردود 13.0%

المذيبات

dioxane

water

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction was degassed with nitrogen (3×)
2. 2
   درجة الحرارةheated at 120° C. (MW) for 1.5 h
3. 3
   workup.ADDITIONthen diluted with EA (10 mL) and water (2 mL)
4. 4
   ترشيحfiltered
5. 5
   تركيزThe filtrate was concentrated to a residue which
6. 6
   أخرىwas purified by Prep TLC
7. 7
   غسيلeluted with PE/EA (2:1)

الإجراء التجريبي

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 (100 mg, 0.19 mmol), 2-isopropyl phenylboronic acid (62.52 mg, 0.38 mmol), NaHCO3 (48 mg, 0.57 mmol), aq. 2M K3PO4 (0.47 ml, 0.94 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) and water (2 mL) and filtered. 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-((4-chlorophenyl)(hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (15 mg, 12.9% yield) as a colorless oil. LCMS: MH+ 608 and TR=2.668 min.

المصدر