反应详情

温度

-30 °C

To a mixture of 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine (3.5 g, 13.8 mmol) and TMEDA (3.1 mL, 20.7 mmol) in THF (100 mL) at −78° C. was added n-BuLi (8.3 mL, 2.5 M in hexanes, 20.7 mmol). The resulting mixture was allowed to warm to −30° C. over 45 min then cooled back to −78° C. before the addition of a solution of 3-oxo-piperidine-1-carboxylic acid tert-butyl ester (4.1 g, 20.7 mmol) in THF (10 mL). The reaction mixture was warmed to r.t. and stirred for 2 h then quenched with H2O and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was triturated with Et2O and unreacted starting material removed by filtration. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 30-80%) then triturated with cyclohexane affording 3-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (5.0 g, 81%). LCMS (method A): RT 3.50 min [M+H]+ 453.3

1. temperatureThe reaction mixture was warmed to r.t.
2. customthen quenched with H2O
3. extractionextracted with EtOAc
4. washThe combined organic phases were washed with brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customThe resulting residue was triturated with Et2O
8. customremoved by filtration
9. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 30-80%)
10. customthen triturated with cyclohexane