Reaktion #88449

Reaktionsgleichung

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

Compound 48

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

3-chlorophenyl boronic acid

K3PO4

→

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

Ausbeute 26.0%

Lösungsmittel

dioxane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction was degassed with nitrogen (3×)
2. 2
   Temperaturheated at 120° C. (MW) for 1.5 h
3. 3
   workup.ADDITIONdiluted with EA (2 mL) and water (2 mL)
4. 4
   Filtrationthen filtered through Celite
5. 5
   EinengenThe filtrate was concentrated to a residue which
6. 6
   Sonstigewas purified by Prep TLC PE/EA (2:1)

Vorschrift

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 (See Compound 48, step 1, 100 mg, 0.212 mmol), 3-chlorophenyl boronic acid (66 mg, 0.424 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, diluted with EA (2 mL) and water (2 mL) then filtered through Celite. The filtrate was concentrated to a residue which was purified by Prep TLC PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenyl)-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 26% yield) as colorless oil. LCMS: MH+ 546 and TR=2.569 min.

Quelle