反应详情

温度

-40 °C

To a mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (2.5 g, 6.88 mmol) and TMEDA (1.6 mL, 10.33 mmol) in THF (40 mL) at −78° C. was added n-BuLi (4.1 mL, 2.5 M in hexanes, 10.33 mmol). The resulting mixture was allowed to warm to −40° C. over 30 min then cooled back to −78° C. before the addition of a solution of 3-oxoazetidine-1-carboxylic acid tert-butyl ester (1.8 g, 10.33 mmol) in THF (10 mL). The reaction mixture was warmed to −10° C. over 2 h then quenched with sat, aq. NH4Cl and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-5%) then recrystallised from iPrOAc and pentane affording 3-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester as a cream solid (2.4 g, 64%). LCMS (method A): RT 2.83 min [M+H]+ 535.4

1. temperatureThe reaction mixture was warmed to −10° C. over 2 h
2. customthen quenched
3. extractionaq. NH4Cl and extracted 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 purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-5%)
8. customthen recrystallised from iPrOAc and pentane