Cesium carbonate → [(S)-1-(7-Cyclopropyl-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine

温度

100 °C

A mixture of [(S)-1-(7-bromo-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine (50 mg, 0.09 mmol), cyclopropylboronic acid (10 mg, 0.12 mmol) and Cs2CO3 (46 mg, 0.14 mmol) in a 4:1 mixture dioxane:water (2.5 mL) was degassed with a stream of argon prior to addition of Pd(PPh3)4 (5 mg) and was heated at 100° C. for 18 h in a sealed vial. Additional cyclopropylboronic acid (10 mg, 0.12 mmol) and Pd(PPh3)4 (5 mg) in dioxane (0.25 mL) were added and stirring at 100° C. in a sealed vial was continued for 3 h. The reaction mixture was diluted with water and extracted with EtOAc (×3). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 25 min gradient 10-90%, 0.1% HCO2H in acetonitrile/water) to afford the title compound (20 mg, 43%). LCMS (Method C): RT 3.32 min [M+H]+ 498.1.

1. customwater (2.5 mL) was degassed with a stream of argon
2. additionto addition of Pd(PPh3)4 (5 mg)
3. extractionextracted with EtOAc (×3)
4. washThe combined organic fractions were washed with brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 25 min gradient 10-90%, 0.1% HCO2H in acetonitrile/water)

ORDレコード

ord-037b8363dec84cf89913f5b951470947

出典データセット

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08653089B2